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1
Lee, Elaine Linda. "Mechanical Conditioning of Cell Layers for Tissue Engineering." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1322758337.
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Banerjee, Tamoghna. "Power Conditioning System on a Micro-Grid System." Scholar Commons, 2019. https://scholarcommons.usf.edu/etd/7736.
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This paper presents renewable energy, power electronics, and distributed generators. The focus is on wind farm generator, photovoltaic cell, and battery bank system. Power Conditioning system improves the performance of a power system. Apart from the benefits of converting between DC/AC, there is adequate control of real power and additional control of economic reactive power. This is possible because of multiple sources in the system.
This project throws light on the basic principle of power system conditioning, its operation and control, and the economic studies.
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Harfman, Todorovic Maja. "Analysis and design of power conditioning systems." [College Station, Tex. : Texas A&M University, 2008. http://hdl.handle.net/1969.1/ETD-TAMU-2721.
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Zhuang, Lihui. "Mechanisms of microenvironmental conditioning in non-Hodgkin's lymphoma." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/6486.
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Tumours are not autonomous transformed cell populations, but rather a society composed of both malignant and normal, including immune, cells that together foster tumour growth and development. Tumour-associated macrophages have been reported to enhance tumour growth, progression and metastasis. In high-grade non-Hodgkin’s lymphomas, prototypically the B-cell neoplasm, Burkitt’s lymphoma (BL), infiltrating macrophages engulf large numbers of apoptotic tumour cells. Evidence suggests that apoptotic BL cells can condition the tumour microenvironment to promote lymphoma development by selectively attracting macrophages while inhibiting neutrophil infiltration and by stimulating macrophages to produce the B-cell growth and survival factor. Tumour cells grow in a hypoxic and nutrient-deficient environment and the resultant cellular stress can induce apoptosis. It is therefore possible that hostile environmental conditions in the tumour also contribute to the generation of a pro-tumour microenvironment. This thesis describes investigations which examined this hypothesis. BL cells were cultured at high density to mimic conditions of metabolic stress existing in the tumour environment. Cell-free supernatants from such stressed BL cells demonstrated potent chemoattractive activity for mononuclear phagocytes. Supernatants from BL cells that were protected from apoptosis by over-expression of bcl-2 had similar ability, confirming that chemoattractant release was apoptosis-independent. The observation that apyrase and suramin could inhibit the chemotactic activity of these supernatants suggested that nucleotides might be the apoptosis-independent chemoattractant. Detection of ATP in stress supernatants by bioluminescence assay was consistent with this proposal. Significantly, supernatants from BL cells and those transfected with bcl-2 were both found to inhibit neutrophil migration, suggesting the occurrence of a neutrophil migration inhibitory factor whose release was apoptosis-independent. Furthermore, stress supernatants could promote BL cell proliferation in vitro, which was apoptosis and cell line-independent. In order to study the role of TAM in the tumour microenvironment, a novel macrophage model was devised using mouse embryonic stem cells (ES cells). Cells derived from ES cells generated in vitro expressed macrophage-specific markers and were free of dendritic cells and undifferentiated ES cells. ES cell-derived macrophages (ESDM) could migrate towards apoptotic BL cells and engulf them. However, ESDM migrated to stress supernatants with decreasing efficiency as they matured. Preliminary data indicated that the phagocytic ability of ESDM to engulf apoptotic cells increased as they matured, consistent with distinct roles for circulating monocytes and tissue macrophages with regard to this function. Considering the high yields and purities of ESDM described here, together with their non-malignant nature and genetic versatility these cells should provide a superior source of undifferentiated mononuclear phagocytes with which to elucidate the molecular mechanisms underlying tumour infiltration and microenvironmental conditioning by TAM. In conclusion, this work suggests that under conditions of pre-apoptotic stress, BL cells have the capacity to regulate their micro-environment upstream of their apoptosis programme to promote net tumour growth through paracrine signals that attract supportive macrophages and inhibit destructive neutrophils and through release of autocrine/juxtacrine tumour growth factors.
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Ren, Aaron G. "Immunosuppressants used in the conditioning regimens for hematopoietic stem cell transplantation /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/7957.
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Di, Federico Erica. "Complex mechanical conditioning of cell-seeded constructs can influence chondrocyte activity." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/7982.
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Articular cartilage represents a primary target for tissue engineering strategies as it does not functionally regenerate within the joint. Many tissue engineering approaches have focused on the in vitro generation of neo-cartilage using chondrocyte-seeded scaffolds. Several studies have reported the morphological appearance of native cartilage, although its functional competence has not been demonstrated. Accordingly, mechanical conditioning has often been introduced to enhance biosynthetic activity of chondrocytes within 3D constructs. However although this strategy has significantly up-regulated proteoglycan synthesis, its effects on the synthesis of the other major solid constituent, type II collagen, has been modest. Analyses of normal joint activities reveal that cartilage is subjected to shear superimposed on uniaxial compression. This complex mechanical state has motivated the design of a biaxial loading system intended for use in vitro to stimulated bovine chondrocytes seeded in agarose constructs. This necessitated the redesign of the construct from cylindrical morphology to accommodate shear loading. The experimental approach was complemented with the development of computational models, which permitted prediction of both cell distortion under biaxial loading regimens and nutrient diffusion within the 3D constructs. An initial study established the profile of proteoglycan and collagen synthesis in free swelling cultures up to day 12. The introduction of dynamic compression (15% strain, 1 Hz for 48 h) enhanced proteoglycan synthesis significantly. In addition, when dynamic shear (10%, 1 Hz) was superimposed on dynamic compression, total collagen synthesis was also up-regulated, within 3 days of culture, without compromising proteoglycan synthesis. Histological analysis revealed marked collagen deposition around individual chondrocytes. However, a significant proportion (50%) of collagen was released into the culture medium, suggesting that it was not fully processed. The overall biosynthetic activity was enhanced more when the biaxial stimulation was applied in a continuous mode as opposed to intermittent loading. The present work offers the potential for a more effective preconditioning of cell-seeded constructs with functional integrity intended for use to resolve defects in joint cartilage.
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Khlid, Ben Hamad. "Fuel cell power conditioning multiphase converter for 1400 VDC megawatts stacks." Thesis, Cape Peninsula University of Technology, 2019. http://hdl.handle.net/20.500.11838/3042.
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Thesis (PhD (Electrical Engineering))--Cape Peninsula University of Technology, 2019Energy systems based on fossil fuel have demonstrated their abilities to permit economic development. However, with the fast exhaustion of this energy source, the expansion of the world energy demand and concerns over global warming, new energy systems dependent on renewable and other sustainable energy are gaining more interests. It is a fact that future development in the energy sector is founded on the utilisation of renewable and sustainable energy sources. These energy sources can enable the world to meet the double targets of diminishing greenhouse gas emissions and ensuring reliable and cost-effective energy supply. Fuel cells are one of the advanced clean energy technologies to substitute power generation systems based on fossil fuel. They are viewed as reliable and efficient technologies to operate either tied or non-tied to the grid to power applications ranging from domestic, commercial to industrial. Multiple fuel cell stacks can be associated in series and parallel to obtain a fuel cell system with high power up to megawatts. The connection of megawatts fuel cell systems to a utility grid requires that the power condition unit serving as the interface between the fuel cell plant and the grid operates accordingly. Different power conditioning unit topologies can be adopted, this study considers a multilevel inverter. Multilevel inverters are getting more popularity and attractiveness as compared to conventional inverters in high voltage and high-power applications. These inverters are suitable for harmonic mitigation in high-power applications whereby switching devices are unable to function at high switching frequencies. For a given application, the choice of appropriate multilevel topology and its control scheme are not defined and depend on various engineering compromises, however, the most developed multilevel inverter topologies include the Diode Clamped, the Flying Capacitor and the Cascade Full Bridge inverters. On the other hand, a multilevel inverter can be either a three or a five, or a nine level, however, this research focuses on the three-level diode clamped inverters. The aim of this thesis is to model and control a three-level diode clamped inverter for the grid connection of a megawatt fuel cell stack. Besides the grid, the system consists of a 1.54 MW operating at 1400 V DC proton exchange membrane fuel cell stack, a 1.26 MW three-level diode clamped inverter with a nominal voltage of 600 V and an LCL filter which is designed to reduce harmonics and meet the standards such as IEEE 519 and IEC 61000-3-6. The inverter control scheme comprises voltage and current regulators to provide a good power factor and satisfy synchronisation requirements with the grid. The frequency and phase are synchronised with those of the grid through a phase locked loop. The modelling and simulation are performed using Matlab/Simulink. The results show good performance of the developed system with a low total harmonic distortion of about 0.35% for the voltage and 0.19% for the current.
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Cochonneau, Stéphanie. "Modulating hematopoietic progenitor cell engraftment and T cell differentiation : role of conditioning and route of administration." Thesis, Montpellier 2, 2012. http://www.theses.fr/2012MON20226.
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Les déficits lymphocytaires T peuvent être corrigés par l'administration en intraveineuse (IV) de cellules souches hématopoiétiques (CSH) provenant d'un donneur. Dans un modèle d'immunodéficience lié à l'absence de la protéine kinase ZAP-70, notre équipe avait précédemment montré que l'injection intrathymique (IT) de CSH histocompatibles conduit à une reconstitution du compartiment T plus robuste et plus rapide que dans le cas où les CSH sont administrées par voie IV. Au cours de ma thèse, je me suis intéressée à l'approche IT dans un contexte non-histocompatible, où j'ai montré que l'injection de CSH semi-allogéniques directement dans le thymus permet le développement d'une thymopoièse à long-terme, même en absence de conditionnement. De plus, j'ai également montré la persistence de progéniteurs thymiques précoces (ETP) provenant du donneur dans le thymus des souris transplantées. De façon remarquable, ces ETP retiennent un potentiel de différenciation plus divers que ceux rencontrés dans le thymus d'une souris sauvage, et leur fréquence est significativement élévée après IT, ce dernier suggérant une disponibilité accrue des niches thymiques. De façon intéressante, j'ai également montré que les progéniteurs déficients en ZAP-70 pouvaient se différencier de façon importante vers le lignage CD8 lors d'une activation constante de la voie de signalisation Notch couplée à la présence d'interleukine 7 (IL-7). Après la greffe de CSH par voie IV de souris ZAP-70-/-, en absence de conditionnemt, j'ai également identifié l'accumulation d'une population de CSH présentant un phénotype particulier (Lin- Sca 1+ c-kit-), nommée LSAPT. Ces cellules LSAPT présentent un biais de différenciation vers le lignage T γδ ainsi qu'une production élevée d'IL-17, ce qui suggère que les fonctions effectrices d'une cellule T γδ sont dépendantes de leur origine progénitrices. L'ensemble de mes résultats apporte à la fois de nouveaux éléments concernant l'identification de progéniteurs T et démontrent de l'influence/coopération entre voies de signalisation et facteurs environnementaux dans la modulation de la différenciation T et de leur fonctions effectricesT cell deficiencies can be corrected by the intravenous (IV) injection of donor hematopoietic stem cells (HSCs). Using a murine model of ZAP-70-/- deficiency, our group previously showed that the intrathymic (IT) administration of histocompatible HSCs leads to a more robust and long-term thymopoiesis as compared to that achieved by the classical IV route. During my PhD, I found that the direct IT administration of semiallogeneic HSCs results in a sustained donor-derived thymopoiesis, overcoming histocompatibility barriers, even in the absence of conditioning. Furthermore, I found that donor-derived early thymic progenitors (ETPs) persist in the thymi of ZAP-70-/- transplanted mice, and present increased multi-lineage potential as compared to wild-type ETPs. Importantly, the frequency of donor-derived ETPs was augmented following IT transplantation, indicative of an increased progenitor niche. Interestingly, ZAP-70-deficient HSC could themselves be driven to a CD8 lineage fate in an environment where IL-7 potentiates continuous activation of the Notch pathway. Following IV transplantation of donor HSC into non-conditioned ZAP-70-/- mice, I determined that there is an accumulation of lineage-/Sca1+ donor progenitors lacking expression of the stem cell marker c-kit, termed LSAPT. These LSAPT show a biased differentiation towards the γδ T cell lineage with high IL-17-producing effector function, suggesting that progenitor origin regulates γδ T cell fate. The ensemble of my experiments provide new insights into the identity of T lineage progenitors and demonstrate how signaling pathways as well as environmental factors modulate T cell differentiation and effector function
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Talay, Oezcan. "Efficient dendritic cell maturation and initiation of a strong T cell immune response requires B7-H1-mediated dendritic cell 'conditioning' during interaction with T cells." [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:16-opus-89195.
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Guyette, Jacques Paul. "Conditioning of Mesenchymal Stem Cells Initiates Cardiogenic Differentiation and Increases Function in Infarcted Hearts." Digital WPI, 2012. https://digitalcommons.wpi.edu/etd-dissertations/32.
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Current treatment options are limited for patients with myocardial infarction or heart failure. Cellular cardiomyoplasty is a promising therapeutic strategy being investigated as a potential treatment, which aims to deliver exogenous cells to the infarcted heart, for the purpose of restoring healthy myocardial mass and mechanical cardiac function. While several cell types have been studied for this application, only bone marrow cells and human mesenchymal stem cells (hMSCs) have been shown to be safe and effective for improving cardiac function in clinical trials. In both human and animal studies, the delivery of hMSCs to infarcted myocardium decreased inflammatory response, promoted cardiomyocyte survival, and improved cardiac functional indices. While the benefits of using hMSCs as a cell therapy for cardiac repair are encouraging, the desired expectation of cardiomyoplasty is to increase cardiomyocyte content that will contribute to active cardiac mechanical function. Delivered cells may increase myocyte content by several different mechanisms such as differentiating to a cardiomyocyte lineage, secreting paracrine factors that increase native stem cell differentiation, or secreting factors that increase native myocyte proliferation. Considerable work suggests that hMSCs can differentiate towards a cardiomyocyte lineage based on measured milestones such as cardiac-specific marker expression, sarcomere formation, ion current propagation, and gap junction formation. However, current methods for cardiac differentiation of hMSCs have significant limitations. Current differentiation techniques are complicated and tedious, signaling pathways and mechanisms are largely unknown, and only a small percentage of hMSCs appear to exhibit cardiogenic traits. In this body of work, we developed a simple strategy to initiate cardiac differentiation of hMSCs in vitro. Incorporating environmental cues typically found in a myocardial infarct (e.g. decreased oxygen tension and increased concentrations of cell-signaling factors), our novel in vitro conditioning regimen combines reduced-O2 culture and hepatocyte growth factor (HGF) treatment. Reduced-O2 culturing of hMSCs has shown to enhance differentiation, tissue formation, and the release of cardioprotective signaling factors. HGF is a pleiotropic cytokine involved in several biological processes including developmental cardiomyogenesis, through its interaction with the tyrosine kinase receptor c-Met. We hypothesize that applying a combined conditioning treatment of reduced-O2 and HGF to hMSCs in vitro will enhance cardiac-specific gene and protein expression. Additionally, the transplantation of conditioned hMSCs into an in vivo infarct model will result in differentiation of delivered hMSCs and improved cardiac mechanical function. In testing our hypothesis, we show that reduced-O2 culturing can enhance hMSC growth kinetics and total c-Met expression. Combining reduced-O2 culturing with HGF treatment, hMSCs can be conditioned to express cardiac-specific genes and proteins in vitro. Using small-molecule inhibitors to target specific effector proteins in a proposed HGF/c-Met signaling pathway, treated reduced-O2/HGF hMSCs show a decrease in cardiac gene expression. When implanted into rat infarcts in vivo, reduced-O2/HGF conditioned hMSCs increase regional cardiac mechanics within the infarct region at 1 week and 1 month. Further analysis from the in vivo study showed a significant increase in the retention of reduced-O2/HGF conditioned hMSCs. Immunohistochemistry showed that some of the reduced-O2/HGF conditioned hMSCs express cardiac-specific proteins in vivo. These results suggest that a combined regimen of reduced-O2 and HGF conditioning increases cardiac-specific marker expression in hMSCs in vitro. In addition, the implantation of reduced-O2/HGF conditioned hMSCs into an infarct significantly improves cardiac function, with contributing factors of improved cell retention and possible increases in myocyte content. Overall, we developed a simple in vitro conditioning regimen to improve cardiac differentiation capabilities in hMSCs, in order to enhance the outcomes of using hMSCs as a cell therapy for the diseased heart.
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Bower, Trent A. "Voltage Self-Amplification and Signal Conditioning for Enhanced Microbial Fuel Cell Performance." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1374234731.
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Valente, Sabrina <1980>. "Vascular wall stem cells. Selection and conditioning of progenitors useful for cell therapy. A pathological case study." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/2857/1/Valente_Sabrina_tesi.pdf.
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The arterial wall contains MSCs with mesengenic and angiogenic abilities. These multipotent precursors have been isolated from variously-sized human adult segments, belying the notion that vessel wall is a relatively quiescent tissue. Recently, our group identified in normal human arteries a vasculogenic niche and subsequently isolated and characterized resident MSCs (VW-MSCs) with angiogenic ability and multilineage potential. To prove that VW-MSCs are involved in normal and pathological vascular remodeling, we used a long-term organ culture system; this method was of critical importance to follow spontaneous 3-D vascular remodeling without any influence of blood cells. Next we tried to identify and localize in situ the VW-MSCs and to understand their role in the vascular remodeling in failed arterial homografts. Subsequently, we isolated this cell population and tested in vitro their multilineage differentiation potential through immunohistochemical, immunofluorescence, RT-PCR and ultrastructural analysis. From 25-30cm2 of each vascular wall homograft sample, we isolated a cell population with MSCs properties; these cells expressed MSC lineage molecules (CD90, CD44, CD105, CD29, CD73), stemness (Notch-1, Oct-4, Sca-1, Stro-1) and pericyte markers (NG2) whilst were negative for hematopoietic and endothelial markers (CD34, CD133, CD45, KDR, CD146, CD31 and vWF). MSCs derived from failed homografts (H-MSCs) exhibited adipogenic, osteogenic and chondrogenic potential but scarce propensity to angiogenic and leiomyogenic differentiation.
The present study demonstrates that failed homografts contain MSCs with morphological, phenotypic and functional MSCs properties; H-MSCs are long-lived in culture, highly proliferating and endowed with prompt ability to differentiate into adipocytes, osteocytes and chondrocytes; compared with VW-MSCs from normal arteries, H-MSCs show a failure in angiogenic and leiomyogenic differentiation. A switch in MSCs plasticity could be the basis of pathological remodeling and contribute to aneurysmal failure of arterial homografts. The study of VW-MSCs in a pathological setting indicate that additional mechanisms are involved in vascular diseases; their knowledge will be useful for opening new therapeutic options in cardiovascular diseases.
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Valente, Sabrina <1980>. "Vascular wall stem cells. Selection and conditioning of progenitors useful for cell therapy. A pathological case study." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/2857/.
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The arterial wall contains MSCs with mesengenic and angiogenic abilities. These multipotent precursors have been isolated from variously-sized human adult segments, belying the notion that vessel wall is a relatively quiescent tissue. Recently, our group identified in normal human arteries a vasculogenic niche and subsequently isolated and characterized resident MSCs (VW-MSCs) with angiogenic ability and multilineage potential. To prove that VW-MSCs are involved in normal and pathological vascular remodeling, we used a long-term organ culture system; this method was of critical importance to follow spontaneous 3-D vascular remodeling without any influence of blood cells. Next we tried to identify and localize in situ the VW-MSCs and to understand their role in the vascular remodeling in failed arterial homografts. Subsequently, we isolated this cell population and tested in vitro their multilineage differentiation potential through immunohistochemical, immunofluorescence, RT-PCR and ultrastructural analysis. From 25-30cm2 of each vascular wall homograft sample, we isolated a cell population with MSCs properties; these cells expressed MSC lineage molecules (CD90, CD44, CD105, CD29, CD73), stemness (Notch-1, Oct-4, Sca-1, Stro-1) and pericyte markers (NG2) whilst were negative for hematopoietic and endothelial markers (CD34, CD133, CD45, KDR, CD146, CD31 and vWF). MSCs derived from failed homografts (H-MSCs) exhibited adipogenic, osteogenic and chondrogenic potential but scarce propensity to angiogenic and leiomyogenic differentiation.
The present study demonstrates that failed homografts contain MSCs with morphological, phenotypic and functional MSCs properties; H-MSCs are long-lived in culture, highly proliferating and endowed with prompt ability to differentiate into adipocytes, osteocytes and chondrocytes; compared with VW-MSCs from normal arteries, H-MSCs show a failure in angiogenic and leiomyogenic differentiation. A switch in MSCs plasticity could be the basis of pathological remodeling and contribute to aneurysmal failure of arterial homografts. The study of VW-MSCs in a pathological setting indicate that additional mechanisms are involved in vascular diseases; their knowledge will be useful for opening new therapeutic options in cardiovascular diseases.
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Sutcliffe, Helen C. "Infiltration and air change studies in large single cell buildings." Thesis, Coventry University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303351.
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De, Villiers Danielle. "The effect of oxidative stress and hypoxic conditioning on mesenchymal stem cell differentiation." Diss., University of Pretoria, 2015. http://hdl.handle.net/2263/53054.
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Introduction
South Africa is ranked the third most obese country after the United States of America and
Great Britain. According to a study conducted by the South African Medical Research Council,
61% of the South African population is overweight, obese, or severely obese. Research into
obesity and its contributing factors has increased as the problem continues to increase on a
global scale. Adipose-derived stromal/stem cells (ASCs), formerly known as mesenchymal
stem cells (MSCs), are obtained from adipose tissue and have self-renewal properties and
multipotential capabilities. A subpopulation of these cells with stem cell characteristics has
the potential to differentiate down the adipogenic lineage. This provides a human primary
cell model to study the mechanisms of adipogenesis including hyperplasia (cell number
proliferation and/or differentiation) and hypertrophy (cell size increase due to lipid droplet
accumulation). The stromal/stem cells are said to reside in hypoxic niches where the
physiological O2 tension is lower than ambient O2 tension (21% O2) and thus oxidative stress
may be reduced. Obesity is correlated with increased oxidative stress and chronic
inflammation. Inflammation is associated with the generation of ROS and the accumulation
of ROS leads to oxidative stress. ROS is also important in signal transduction pathways.
Adipogenesis is triggered by signaling molecules leading to the conversion of a
subpopulation of ASCs to preadipocytes, which further differentiate into mature adipocytes.
Differentiation down specific lineages coincides with the migration of these stromal/stem
cells out of the hypoxic niche. This motivated the assessment of the effect of oxidative stress
and a hypoxic mimetic, Dimethyloxalylglycine (DMOG) on adipogenesis in vitro.
Methods
ASCs were induced to differentiate into adipocytes using adipogenic-inducing medium. The
use of the pro-oxidant, H2O2, and the antioxidants, Trolox and CoQ10 allowed for the
modulation of ROS in the ASC cultures. Hypoxia was mimicked by the addition of DMOG to
ASCs that were induced to differentiate into adipocytes. The adipogenic differentiation was
quantitatively detected using flow cytometry and the emission profiles of Nile Red.
Results
It was demonstrated that ROS added exogenously to adipogenic-induced ASCs enhanced
adipogenesis. It was also observed that H2O2 added to non-induced ASCs caused lipid
accumulation. Trolox and CoQ10 attenuated the increase in ROS and thus a decrease in
adipogenesis was seen. Removal of pyruvate, a ROS scavenger, was necessary to see these effects. The addition of DMOG resulted in a trend towards the reduction in adipogenesis over
the 14 and 21-day induction periods.
Conclusion
ASCs provide a primary cell model for investigating adipogenesis and the effects of oxidative
stress and hypoxia on this process. This is relevant for many diseases and therapeutic
options. The study also showed that flow cytometry is a powerful technique that can aid in
the quantitative detection of adipogenesis and the cell sub-populations that make up this
process. This research underscores the importance of assessing the effects of both oxidative
stress and hypoxia on adipogenesis at a gene and protein level in the future.Dissertation (MSc)--University of Pretoria, 2015.
Immunology
MSc
Unrestricted
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Malo, Barragán Shane Leonardo. "Design and Control of an Electric Energy Conditioning System for a PEM Type Fuel Cell." Doctoral thesis, Universitat Politècnica de Catalunya, 2009. http://hdl.handle.net/10803/5957.
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Isolated electric energy generation systems are often needed to supply electric loads where the electrical network is not available. This could be caused due to geographic isolation, the necessity of load mobility, demanded values of voltage and current that are not compatible with the local networks, etc. This makes the design and construction of stand-alone energy generation systems a must.Modern designs are being pushed towards cleaner technologies. The experience has shown that the usual methods employed to produce electrical energy are not sustainable, especially because of environmental concerns. Usual stand-alone energy generation systems employ batteries and fuel engines. Batteries offer a cheap mean to feed the generation system but need rigorous maintenance routines, the substances used in their construction are strong pollutants, offer relatively low durability and the ratio charge time/discharge time is too high. Fuel engines extract their energy from petroleum based fuels, and as its well known, pollute their surrounding environment in several ways producing smoke, noise and heat.
Polymer electrolyte membrane type fuel cells are among the new technologies that are being considered as a good alternative to the traditional power sources used for stand-alone energy generation systems.
AIthough the basic principles of operation of the fuel cells are known since 1839, this is a technology that is far from being mature. More work needs to be done in order to make of the fuel cells systems with, high reliability, with maximum efficiency, and capable of providing electrical energy with quality comparable to the quality achieved using usual methods.
The problems when working with fuel cells can be split in two big groups of interest, the first, being the handling and control of the electrochemical variables, and the second, the handling and control of the electrical variables taking care of the limits imposed by the dynamics of the fuel cell unit. This work deals with the second group of concerns, looking at the fuel cell as a black-box dc power supply with certain current/voltage characteristics. The energy provided by the fuel cells needs to be conditioned to the levels and characteristics required by the loads to be fed. In Europe, for single-phase ac loads, the specifications are a sinusoidal output voltage with 230 V ac rms and a frequency of 50 Hz. This work presents the the analysis, design, construction, and control of the electric energy conditioning system for a polymer eIectrolyte membrane type fuel cell to act as an stand-alone dc-ac inverter to feed linear or nonlinear loads with big variations.
Los sistemas de generación de energía eléctrica "en isla" son necesarios en muchas ocasiones para alimentar cargas donde la red eléctrica no está disponible. Esto puede deberse a diversos factores como: aislamiento geográfico, necesidad de movilidad de la carga, requerimientos de corriente y voltaje que no son compatibles con las redes locales, etc. Todas estas razones hacen del diseño y construcción de sistemas autónomos de generación de energía una necesidad.
En la actualidad, los diseños de este tipo de dispositivos están tendiendo hacia tecnologías más limpias.
La experiencia ha enseñado que los métodos habituales para producir energía eléctrica no son los más apropiados, especialmente por motivos medioambientales. Los sistemas autónomos de generación de energía eléctrica típicos utilizan baterías y máquinas de combustión. Las baterías ofrecen una fuente barata para alimentar el sistema de generación de energía eléctrica, pero necesitan de rigurosas rutinas de mantenimiento, algunas de las sustancias utilizadas en su construcción son altamente contaminantes, ofrecen una relativamente baja durabilidad y la razón tiempo de carga/tiempo de descarga es grande.
Por otro lado, las máquinas de combustión extraen la energía de combustibles a base de petróleo, como es bien conocido, contaminan el entorno produciendo humo, ruido y calor.
Las pilas de combustible de membrana de electrolito polimérico están entre las nuevas tecnologías que se consideran como una buena alternativa a las fuentes que se utilizan usualmente para alimenta sistemas autónomos de generación de energía. Aunque los principios básicos de operación de las pilas de combustible son conocidos desde 1839, esta es una tecnología que está aún lejos de pode considerarse madura. Aún es necesario realizar más esfuerzos con el objetivo de hacer de las pilas de combustible fuentes de energía de alta confiabilidad, de máxima eficiencia y capaces de proveer energía con niveles de calidad comparables a los alcanzados al utilizar los métodos tradicionales.
La problemática que se presenta al trabajar con pilas de combustible puede ser dividida en dos grandes grupos de interés, el primero, sería el control de las variables electroquímicas, y el segundo, el manejo control de las variables eléctricas tomando en cuenta los límites impuestos por la dinámica de la pila de combustible. Éste trabajo trata con el segundo, viendo la pila de combustible como una "caja negra" que constituye una fuente de potencia de corriente continua con ciertas características particulares de voltaje/corriente. La energía provista por la pila de combustible debe ser acondicionada a los niveles características requeridas por las cargas a ser alimentadas. En Europa, para sistemas de monofásico de corriente alterna, las especificaciones son un voltaje sinusoidal con 230 V efectivos y una frecuencia de 50 Hz. Éste trabajo presenta el análisis, diseño, construcción y control del sistema de acondicionamiento de energía eléctrica para una pila de combustible de membrana de electrolito polimérico, que actúa como un sistema autónomo de inversión de corriente continua-corriente alterna para alimentar cargas lineales o no lineales que pueden experimentar grandes variaciones.
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Song, Yu Jin. "Analysis and design of high frequency link power conversion systems for fuel cell power conditioning." Diss., Texas A&M University, 2004. http://hdl.handle.net/1969.1/2678.
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In this dissertation, new high frequency link power conversion systems for the fuel cell power conditioning are proposed to improve the performance and optimize the cost, size, and weight of the power conversion systems. The first study proposes a new soft switching technique for the phase-shift controlled bi-directional dc-dc converter. The described dc-dc converter employs a low profile high frequency transformer and two active full-bridge converters for bidirectional power flow capability. The proposed new soft switching technique guarantees soft switching over wide range from no load to full load without any additional circuit components. The load range for proposed soft switching technique is analyzed by mathematical approach with equivalent circuits and verified by experiments. The second study describes a boost converter cascaded high frequency link direct dc-ac converter suitable for fuel cell power sources. A new multi-loop control for a boost converter to reduce the low frequency input current harmonics drawn from the fuel cell is proposed, and a new PWM technique for the cycloconverter at the secondary to reject the low order harmonics in the output voltages is presented. The performance of the proposed scheme is verified by the various simulations and experiments, and their trade-offs are described in detail using mathematical evaluation approach. The third study proposes a current-fed high frequency link direct dc-ac converter suitable for residential fuel cell power systems. The high frequency full-bridge inverter at the primary generates sinusoidally PWM modulated current pulses with zero current switching (ZCS), and the cycloconverter at the secondary which consists of only two bidirectional switches and output filter capacitors produces sinusoidally modulated 60Hz split single phase output voltage waveforms with near zero current switching. The active harmonic filter connected to the input terminal compensates the low order input current harmonics drawn from the fuel cell without long-term energy storage devices such as batteries and super capacitors.
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Weckerle, Christoph [Verfasser], and André [Akademischer Betreuer] Thess. "A metal hydride air-conditioning system for fuel cell vehicles / Christoph Weckerle ; Betreuer: André Thess." Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2020. http://d-nb.info/1219905828/34.
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Miwa, Hidekazu. "High-Efficiency Low-Voltage High-Current Power Stage Design Considerations for Fuel Cell Power Conditioning Systems." Thesis, Virginia Tech, 2009. http://hdl.handle.net/10919/42519.
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Fuel cells typically produce low-voltage high-current output because their individual cell voltage is low, and it is nontrivial to balance for a high-voltage stack. In addition, the output voltage of fuel cells varies depending on load conditions. Due to the variable low voltage output, the energy produced by fuel cells typically requires power conditioning systems to transform the unregulated source energy into more useful energy format. When evaluating power conditioning systems, efficiency and reliability are critical. The power conditioning systems should be efficient in order to prevent excess waste of energy. Since loss is dissipated as heat, efficiency directly affects system reliability as well. High temperatures negatively affect system reliability. Components are much more likely to fail at high temperatures. In order to obtain excellent efficiency and system reliability, low-voltage high-current power conditioning systems should be carefully designed.
Low-voltage high-current systems require carefully designed PCB layouts and bus bars. The bus bar and PCB trace lengths should be minimized. Therefore, each needs to be designed with the other in mind. Excessive PCB and bus bar lengths can introduce parasitic inductances and resistances which are detrimental to system performance. In addition, thermal management is critical. High power systems must have sufficient cooling in order to maintain reliable operation.
Many sources of loss exist for converters. For low-voltage high-current systems, conduction loss and switching loss may be significant. Other potential non-trivial sources of loss include magnetic losses, copper losses, contact and termination losses, skin effect losses, snubber losses, capacitor equivalent series resistance (ESR) losses, and body diode related losses. Many of the losses can be avoided by carefully designing the system. Therefore, in order to optimize efficiency, the designer should be aware of which components contribute significant amounts of loss. Loss analysis may be performed in order to determine the various sources of loss. The system efficiency can be improved by optimizing components that contribute the most loss.
This thesis surveys some potential topologies suitable for low-voltage high-current systems. One low-voltage high-current system in particular is analyzed in detail. The system is called the V6, which consists of six phase legs, and is arranged as a three full-bridge phase-shift modulated converter to step-up voltage for distributed generation applications. The V6 converter has current handling requirements of up to 120A. Basic operation and performance is analyzed for the V6 converter. The loss within the V6 converter is modeled and efficiency is estimated. Calculations are compared with experimental results. Efficiency improvement through parasitic loss reduction is proposed by analyzing the losses of the V6 converter. Substantial power savings are confirmed with prototypes and experimental results. Loss analysis is utilized in order to obtain high efficiency with the V6 converter. Considerations for greater current levels of up to 400A are also discussed. The greater current handling requirements create additional system issues. When considering such high current levels, parallel devices or modules are required. Power stage design, layout, and bus bar issues due to the high current nature of the system are discussed.Master of Science
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Darling, Ryan Daniel. "Single Cell Analysis of Hippocampal Neural Ensembles during Theta-Triggered Eyeblink Classical Conditioning in the Rabbit." Miami University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=miami1225460517.
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Niu, Xianzhi. "The functional role of the lateral olivocochlear system and mechanisms underlying sound conditioning /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-094-X/.
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Park, Sung Yeul. "A Wide Range and Precise Active and Reactive Power Flow Controller for Fuel Cell Power Conditioning Systems." Diss., Virginia Tech, 2009. http://hdl.handle.net/10919/28645.
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This dissertation aims to present a detailed analysis of the grid voltage disturbance in frequency domain for the current control design in the grid-tie inverter applications and to propose current control techniques in order to minimize its impact and maximize feasibility of the power conditioning system in distributed generations. Because the grid voltage is constantly changing, the inverter must be able to response to it. If the inverter is unable to respond properly, then the grid voltage power comes back to the system and damages the fuel cell power conditioning systems.
A closed-loop dynamic model for the current control loop of the grid-tie inverter has been developed. The model explains the structure of the inverter admittance terms. The disturbance of the grid voltages has been analyzed in frequency domain. The admittance compensator has been proposed to prevent the grid voltage effect. The proposed lead-lag current control with admittance compensator transfers current properly without system failure. In order to get rid of the steady-state error of the feedback current, a proportional-resonant controller (PR) has been adopted. A PR control with admittance compensation provides great performance from zero power to full power operation. In addition, active and reactive power flow controller has been proposed based on the PR controller with admittance compensation. The proposed active and reactive power flow control scheme shows a wide range power flow control from pure leading power to pure lagging power. Finally, the proposed controller scheme has been verified its feasibility in three phase grid-tie inverter applications. First of all, a half-bridge grid-tie inverter has been designed with PR controller and admittance compensation. Then three individual grid-tie inverters has been combined and produced three phase current to the three phase grid in either balanced condition or unbalanced condition.
The proposed control scheme can be applied not only single phase grid-tie inverter application, but also three phase grid-tie inverter application. This research can be applicable to the photovoltaic PCS as well. This technology makes renewable energy source more plausible for distributed generations.Ph. D.
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Omazic, Brigitta. "Immune reconstitution after allogeneic hematopoietic stem cell transplantation /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-117-2/.
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Seliktar, Dror. "Dynamic mechanical conditioning regulates the development of cell-seeded collagen constructs in vitro : implications for tissue-engineered blood vessels." Diss., Georgia Institute of Technology, 2000. http://hdl.handle.net/1853/25674.
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Flowers, Christopher R., Luciano J. Costa, Marcelo C. Pasquini, Jennifer Le-Rademacher, Michael Lill, Tsiporah B. Shore, William Vaughan, et al. "Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes." ELSEVIER SCIENCE INC, 2016. http://hdl.handle.net/10150/621283.
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Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.
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Hentschke, Patrik. "Anti-tumour effect in solid tumours, tolerance and immune reconstitution after allogeneic haematopoietic stem cell transplantation /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-800-9/.
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Hassan, Zuzana. "Studies on mechanisms of busulphan cytotoxicity and pharmacokinetics : with special reference to liposomal busulphan /." Stockholm : Karoliska Univ. Press, 2001. http://diss.kib.ki.se/2001/20010504hass/.
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Langford-Smith, Kia Jane. "Non-myeloablative bone marrow transplantation for Mucopolysaccharide diseases." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/nonmyeloablative-bone-marrow-transplantation-for-mucopolysaccharide-diseases(5d3fd9c5-01f2-42aa-81ed-a2ce6ef140fe).html.
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The Mucopolysaccharide (MPS) diseases are a group of lysosomal storage disorders, caused by a lack of the enzymes required for catabolism of glycosaminoglycans (GAGs), leading to severe neurological decline, skeletal deformities, organomegaly, cardiac and respiratory compromise, and premature death. The severe form of MPS I, Hurler syndrome, can be successfully treated using haematopoietic stem cell transplantation (HSCT), but the risks associated with myeloablation and immune suppression limit the broader application of HSCT to attenuated diseases. Successful engraftment in MPS I has been difficult to achieve, and requires fully myeloablative conditioning, whilst reduced intensity conditioning is a risk factor for graft rejection. Non-myeloablative conditioning generating reliable graft acceptance and high donor chimerism could increase safety and applicability of HSCT in genetic disease, therefore the aim of this research was to identify such a regimen in a clinically relevant mouse model of HSCT.Conditioning regimens developed in existing mouse models of HSCT have had limited clinical success, and often require clinically unachievable high cell doses or less stringent strain combinations to overcome allogeneic transplant rejection. To improve clinical relevance we used CBA donors and C57BL/6 recipients, which require full myeloablation with busulfan and immune suppression using non-depleting anti-CD4 and anti-CD8 monoclonal antibodies for engraftment of low cell doses across a major histocompatibility complex barrier. In syngeneic transplant donor chimerism was improved by generating a greater ratio of donor:recipient haematopoietic cells in the bone marrow initially, therefore we tested granulocyte colony stimulating factor (G-CSF), high cell dose and stem cell niche disruption and compared this to anti-CD40L costimulatory blockade in allogeneic transplant performed with a reduced dose of busulfan that was insufficient for graft acceptance. Despite improvements in initial engraftment with some of these treatments, only combined signal 1 and 2 T cell blockade were effective in reducing the dose of busulfan required for long-term graft acceptance. Early detection of MPS is important in treatment success; good disease biomarkers are vital, and biomarkers suitable for monitoring treatment outcome in MPS are lacking. We evaluated serum heparin cofactor II-thrombin (HCII-T) complex for MPS. We determined optimal sample collection and storage conditions, assay limitations and developed measurement in dried blood spots. Dermatan sulphate has a greater effect on in vivo HCII-T complex formation than heparan sulphate, thus in the MPS mouse models HCII-T is a reliable biomarker for MPS I, but not MPS IIIA or IIIB. HCII-T is greatly elevated in MPS I, II and VI patients, who all store dermatan sulphate, but it is also elevated by a small but significant amount in MPS III patients, who store heparan sulphate. HCII-T was also measured longitudinally in MPS I, II and VI patients, compared to an existing clinical biomarker, and validated against clinical outcomes to show that it is a good biomarker of short-term treatment outcomes and responds rapidly to perturbations in treatment. Finally, we determined whether an engraftment defect was observed in the MPS I mouse model, and show that this is present following both syngeneic and allogeneic HSCT. The effect of enzyme replacement therapy (ERT) and anti-inflammatory treatment prior to allogeneic HSCT was investigated, and initial results suggest that ERT, but not ibuprofen, may improve HSCT outcome. Overall, a clinically relevant mouse model of allogeneic HSCT has been developed and used to determine a non-myeloablative conditioning regimen that generates high levels of donor chimerism with a minimal dose of busulfan and blockade of both signal 1 and 2 of T cell activation. The conditions required to observe an engraftment defect in MPS I mice have also been defined, and preliminary studies have suggested that ERT, but not anti-inflammatory treatment, may overcome the engraftment defect in MPS I. Alongside this work, the HCII-T biomarker has been evaluated in MPS mouse models and patients, determining that it correlates well with short-term treatment outcomes. The techniques and models developed here will provide an excellent basis for further work in developing non-myeloablative conditioning for bone marrow transplant in MPS I.
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Aksoy, Can Aksoy. "Fuel consumption measurements and fuelconditioning in high-pressure fuel systemfor single cylinder test cell." Thesis, Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-75439.
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This master thesis is part of a bigger project issued by AVL with the purpose to design a high pressure compression ignition fuel system for their single cylinder test cell at their facility in Södertälje. Typically compression-ignition fuel tests are being run within an operating pressure range of 500-2400 bar, but this system has to be able to run with pressures up to 3500 bar. The project was intended to be carried out by two participants where this master thesis covers the evaluation of how fuel consumption rates shall be measured in the system described above as well as how the fuel shall be conditioned. The selected concept for measuring fuel consumption rate was based on measuring the mass flow on the low-pressure side of the system with a Coriolis flowmeter. The chosen temperature sensor for monitoring the temperature on the high-pressure side was a K-type thermocouple which would be directly connected to the fuel rail in the system. A bleeder was selected on the basis that it had been used in one of AVL's old test cells. A heat exchanger could not be chosen. However a rough estimation of the capacity needed for a heat exchanger was calculated for future reference. The methodology used to develop a concept was based on the engineering project process taught to students at Karlstad University. First a project plan was made followed by a solution-independently expressed product specification including a specification of requirements and QFD-matrix. Several concepts were generated for measuring the fuel consumption by evaluating different measuring principles, available components, possible positions of the components within the system and combinations with different fuel supply concepts. Less extensive methods were used for the remaining tasks in the detailed engineering phase of the project. The concepts were compared using Pugh's analysis and a concept was selected in collaboration with AVL. The majority of the objectives for this master thesis could be successfully carried out. The documentation and drawings requested by the client, manufacturing of the system, implementation and validation into the test cell could not be done due to lack of time. This, along with the selection of a heat exchanger and low-pressure thermocouple was left for future work.
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Bayer, Wildberger Alexandra Clarissa. "Therapeutic approach for Myasthenia Gravis using conditioned mesenchymal stromal cells." Electronic Thesis or Diss., Sorbonne université, 2022. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2022SORUS528.pdf.
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Inflammatoires telles que l'interféron-γ (IFN-γ), qui peuvent altérer la physiologie et l'immunogénicité cellulaires. Notre équipe a développé une approche alternative consistant à co-cultiver les CSM avec des cellules mononucléées du sang périphérique (PBMC), et a montré que l’injection de cellules conditionnées de qualité recherche induit des améliorations cliniques dans un modèle murin humanisé (NSG-MG).Ici, dans une perspective clinique, nous avons d’abord validé l’utilisation de CSM de qualité clinique. Puis nous avons caractérisé l'expression génique et le profil phénotypique en comparant cellules non stimulées (CSMr), conditionnées (CSMc) ou stimulées par l’IFN-γ (CSMγ), et déduit leurs signatures spécifiques. Nous avons étudié leurs capacités fonctionnelles in vitro et in vivo, et identifié, dans leurs sécrétomes, des molécules potentiellement responsables du conditionnement et de l’immunomodulation. L'étude RNAseq a montré que les conditionnements par PBMC et IFN-γ dérégulaient l'expression de 244 gènes et 2089 gènes, respectivement, par rapport au profil des CSMr. Les CSMc surexprimaient CD26, CD273, CCL11, TNIP1 et TNIP3, et sous-exprimaient CILP et LGALS1. Les CSMγ surexprimaient IDO-1, TGF-β1, CXCL9, CXCL10, et des molécules d’HLA ou associées, comme attendu. Les principales voies de signalisation liées au CSMc comprenaient le remodelage de la matrice extracellulaire, la signalisation par des interleukines et l'immunosuppression, tandis que les voies de la réponse IFN-γ, la signalisation JAK-STAT et la réponse inflammatoire étaient associées aux CSMγ. Les signatures génétiques pour chaque traitement ont été validées par qPCR. Des différences phénotypiques ont été observées entre CSMc, CSMγ et CSMr. La signature de CSMc incluait une augmentation de CD54, CD273 et CD49a, sans modulation des HLA. Au contraire, l'expression de CD317, CD54 et HLA était augmentée en CSMγ. Les profils de regroupements étudiés par cytométrie de masse ont révélé 10 métaclusters. Les CSMr et les CSMc avaient des profils proches, à l'exception d'un cluster caractérisé par une forte empreinte immunomodulatrice, tandis que les CSMγ ont montré un profil complètement différent. Sur le plan fonctionnel le milieu conditionné (MC) des CSMc avait des capacités immunosuppressives in vitro plus puissantes sur la prolifération des cellules T que le MC des CSMr et CSMγ, et augmentait plus efficacement le pourcentage de Tregs. In vivo, les CSMc ont réduit de manière significative le score clinique des souris NSG-MG par rapport aux souris non traitées, dès la deuxième semaine post-injection. Enfin, l'analyse protéomique des MC produits par les PBMC seules, les CSMr seules et leurs cocultures a identifié 22 molécules potentiellement impliquées dans le conditionnement cellulaire, tandis que l’analyse du MC produit par les CSMc a identifié 44 molécules potentiellement impliquées dans l’immunomodulation. Ces résultats permettent de proposer des mécanismes d'action du conditionnement par les PBMC, et suggèrent l'utilisation des CSMc ou de leur MC pour réaliser une immunomodulation dans le cadre de la MG ou d'autres maladies auto-immunesMyasthenia gravis (MG) is a rare autoimmune disease mediated by pathogenic antibodies targeting neuromuscular endplate molecules, mainly the acetylcholine receptor, and characterized by immune deregulation and chronic cell activation. The impaired neuromuscular transmission leads to muscular weakness and invalidating fatigability, and MG crisis can be life-threatening. The treatments are associated with serious side effects, mandating the research of innovative therapeutic solutions. Mesenchymal Stem Cells (MSC) are multipotent progenitor cells possessing broad immunoregulatory capacities, and acting via cell-cell contacts, exosomes production and secretion of soluble mediators. To boost their immunosuppressive capacities, MSCs can be licensed by high doses of pro-inflammatory cytokines such as interferon-γ (IFN-γ), which however may impact MSC fitness and immunogenicity. Our team developed an alternative approach, in which MSC are cocultured with peripheral blood mononuclear cells (PBMC), thus becoming conditioned MSC. The transfer of research grade (RG) cMSC improved the clinical outcomes in a humanized MG mouse model. In a clinical perspective, RG MSC were first replaced by clinical grade MSC, and ideally, the use of PBMC should be replaced by a molecular cocktail. Here, we characterized thoroughly gene expression, phenotypic profile, and secretome changes induced by PBMC conditioning (cMSC), when compared to non-stimulated (rMSC) and IFN-γ stimulated (γMSC) cells. We studied the functional capacities of these cells in vitro and in vivo. Additionally, we identified molecules produced during cell coculture that may be responsible of MSC conditioning. RNAseq study showed that compared to rMSC gene expression profile, conditioning by PBMC deregulated the expression of 244 genes. Compared to rMSC and γMSC, the signature of cMSC included upregulation of CD26, CD273, CCL11, TNIP1 and TNIP3, and downregulation of CILP and LGALS1. γMSC deregulated 2089 genes, harboring a classical signature consisting in up-regulation of IDO-1, TGF-b1, CXCL9, CXCL10, HLA and HLA-associated molecules. Main pathways related to cMSC were extracellular matrix remodeling, signaling by interleukins and immunosuppression, while IFN-γ response, JAK-STAT signaling and inflammatory response were associated with MSC. Gene signatures for each treatment where confirmed by qPCR. cMSC and γMSC also presented phenotypic differences when compared to rMSC. Signatures of cMSC included increased CD54, CD273 and CD49a expression, without HLA modulation. At variance, IFN-γ activation increased expression of CD317, CD54 and HLA molecules. General phenotypic profile studied by mass cytometry revealed 10 different metaclusters; rMSC and cMSC had close profiles, sharing most of the metaclusters except for one that was characterized by a strong immunomodulatory imprint. γMSC showed a completely different phenotypic profile. Regarding functional capacities, in vitro, conditioned medium (CM) produced by cMSC had higher immunosuppressive capacities on T cell proliferation and induced higher percentage of Tregs when compared to rMSC and γMSC CM. The analysis of cMSC secretome revealed 44 molecules that were significantly upregulated by cellular conditioning. In our NSG-MG mouse model, cMSC reduced significantly the clinical score of mice when compared to untreated ones, 2 weeks after injection till end-point of the experiment. Finally, proteomic analysis of soluble factors secreted by PBMC alone, MSC alone and both cells in coculture allowed the identification of 22 molecules that are potentially implicated in cellular conditioning. These results provide clues for defining the mechanisms of action of conditioning by PBMC, and suggest the use of cMSC or their CM to operate immunomodulation in the context of MG, or other auto-immune diseases
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Madasu, Sharath Chandra. "The Metabotropic glutamate receptor mGluR1 regulates the voltage-gated potassium channel Kv1.2 through agonist-dependent and agonist-independent mechanisms." ScholarWorks @ UVM, 2019. https://scholarworks.uvm.edu/graddis/982.
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The voltage gated potassium channel Kv1.2 plays a key role in the central nervous system and mutations in Kv1.2 cause neurological disorders such as epilepsies and ataxias. In the cerebellum, regulation of Kv1.2 is coupled to learning and memory. We have previously shown that blocking Kv1.2 by infusing its specific inhibitor tityustoxin-kα (TsTX) into the lobulus simplex of the cerebellum facilitates eyeblink conditioning (EBC) and that EBC itself modulates Kv1.2 surface expression in cerebellar interneurons. The metabotropic glutamate receptor mGluR1 is required for EBC although the molecular mechanisms are not fully understood. Here we show that infusion of the mGluR1 agonist (S)-3,5-dihydroxyphenylglycine (DHPG) into the lobulus simplex of the cerebellum mimics the facilitating effect of TsTX on EBC. We therefore hypothesize that mGluR1 could act, in part, through suppression of Kv1.2. Earlier studies have shown that Kv1.2 suppression involves channel tyrosine phosphorylation and endocytocytic removal from the cell surface. In this study we report that an excitatory chemical stimulus (50mM K+-100µM glutamate) applied to cerebellar slices enhanced Kv1.2 tyrosine phosphorylation and that this increase was lessened in the presence of the mGluR1 inhibitor YM298198. More direct evidence for mGluR1 modulation of Kv1.2 comes from our finding that selective activation of mGluR1 with DHPG reduced the amount of surface Kv1.2 detected by cell surface biotinylation in cerebellar slices. To determine the molecular pathways involved we used an unbiased mass spectrometry-based proteomics approach to identify Kv1.2-protein interactions that are modulated by mGluR1. Among the interactions enhanced by DHPG were those with PKC-γ, CaMKII, and Gq/G11, each of which had been shown in other studies to co-immunoprecipitate with mGluR1 and contribute to its signaling. Of particular note was the interaction between Kv1.2 and PKC-γ since in HEK cells and hippocampal neurons Kv1.2 endocytosis is elicited by PKC activation. We found that activation of PKCs with PMA reduced surface Kv1.2, while the PKC inhibitor Go6983 attenuated the reduction in surface Kv1.2 levels elicited by DHPG and PMA, suggesting that the mechanism by which mGluR1 modulates cerebellar Kv1.2 likely involves PKC.
mGluR1 has been shown to signal independently of the agonist through a constitutively active, protein kinase A-dependent pathway in the cerebellum. Using HEK293 cells we show that co-expression of mGluR1 increases the surface expression levels of Kv1.2. This effect occurs in absence of mGluR1 agonists and in the presence of a noncompetitive mGluR1 inhibitor YM298198. Co-expression of known downstream effectors of the agonist driven mGluR1 pathway such as PKC-γ, CaMKIIα, Grid2 had no effect on Kv1.2 surface expression or on the ability of mGluR1 agonist to modulate that expression. In contrast, the inverse agonist BAY 36-7620 significantly reduced the mGluR1 effect on Kv1.2 surface expression, as did pharmacological inhibition of PKA with KT5720.
Therefore, mGluR1 is involved in regulation of surface Kv1.2 via dual mechanisms, the agonist dependent mechanism reduces surface Kv1.2 via PKC, while agonist independent constitutive mechanism increases surface Kv1.2 via PKA.
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Raucci, Larissa Moreira Spinola de Castro. "Osteogênese in vitro sobre vitrocerâmica 100% cristalina e altamente bioativa (Biosilicato®): efeitos do condicionamento de superfície e dos produtos de dissolução iônica." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/58/58137/tde-26032010-164221/.
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O objetivo deste estudo foi avaliar o efeito do condicionamento de superfície de uma vitrocerâmica 100% cristalina e altamente bioativa (Biosilicato®) e de seus produtos de dissolução iônica sobre diferentes parâmetros do desenvolvimento do fenótipo osteogênico in vitro. Previamente ao plaqueamento de células osteogênicas de calvárias de ratos, discos de Biosilicato® foram condicionados, por 3 dias, em meio de cultura suplementado, com ou sem soro fetal bovino a 10%. Células osteogênicas expostas aos produtos de dissolução iônica do Biosilicato® foram também cultivadas sobre lamínulas de vidro bioinerte. Discos de Biosilicato e lamínulas de vidro foram utilizados como controles. Os resultados mostraram que o tratamento de superfície de Biosilicato® aumenta expressivamente a concentração de silício e cálcio no meio de cultura. Em 1, 3 e 7 dias, foram determinados os maiores valores de viabilidade celular em superfícies de Biosilicato® condicionado, enquanto que entre os grupos de lamínulas de vidro, observou-se menor viabilidade em culturas expostas aos produtos de dissolução iônica do Biosilicato®. Em 3 dias, células sobre todas as superfícies de Biosilicato® apresentavam-se menos espraiadas quando comparadas àquelas sobre lamínulas de vidro; neste período, a topografia das superfícies dos grupos de Biosilicato® caracterizava-se por rede de cavidades na submicro e nanoescala, enquanto que a lamínula apresentava superfície plana. Alterações no padrão de marcação das proteínas citoesqueléticas actina, vimentina, tubulina e vinculina, da subunidade de integrina α5 e da fibronectina eram observadas apenas em células crescidas sobre as superfícies de Biosilicato®. Ao final da fase proliferativa (7 dias), foram observados maiores níveis relativos de expressão de RNA mensageiro para Runx2, sialoproteína óssea (BSP) e fosfatase alcalina (ALP) em culturas crescidas sobre superfícies condicionadas de Biosilicato®; a exposição aos produtos de dissolução iônica aumentou a expressão de Runx2 e ALP nos grupos de lamínula de vidro. Em 14 dias, culturas sobre Biosilicato® condicionado em meio de cultura com soro exibiam áreas mais extensas de mineralização. Os resultados deste estudo mostraram que o condicionamento de superfícies de Biosilicato® previamente ao plaqueamento celular favorece aspectos da interação célula-substrato, promovendo maior viabilidade celular e aumentando e/ou acelerando o desenvolvimento do fenótipo osteogênico in vitro. A exposição aos produtos de dissolução iônica do Biosilicato® inibe a progressão de culturas osteogênicas sobre lamínulas de vidro bioinerte, apesar de aumentar a expressão de marcadores osteoblásticos.The aim of the present study was to evaluate the effect of surface conditioning of a highly bioactive, fully crystalline glass-ceramic in the Na2O-CaO-SiO2-P2O5 system (Biosilicate®) and of its ionic dissolution products on key parameters of the development of the osteogenic phenotype in vitro. Rat calvaria-derived osteogenic cells were plated on Biosilicate® discs that were pre-conditioned either with supplemented culture medium or serum-free medium for 3 days. In addition, osteogenic cells grown on bioinert glass coverslips were exposed to the ionic dissolution products of the Biosilicate®. The results showed that the supplemented culture medium used for the Biosilicate® surface conditioning exhibited a high concentration silicium and calcium. At 1, 3, and 7 days, cell viability was significantly higher for the conditioned Biosilicate® sufaces, whereas reduced cell viability was observed for cultures grown on glass coverslips and exposed to the ionic dissolution products of Biosilicate®. At day 3, cells grown on Biosilicate® groups were less spread compared with those on glass coverslips. At the same time point, whereas the surface topography of glass coverslips was smooth, Biosilicate® discs exhibited a network of submicron and nanoscale pits. Changes in the labeling pattern of the cytoskeleton proteins actin, vimentin, tubulin and vinculin, and of α5 integrin and fibronectin were only observed for cells grown on Biosilicate® surfaces. At the end of the proliferative phase (day 7), expression levels of Runx2, alkaline phosphatase (ALP) and bone sialoprotein (BSP) mRNAs were significantly higher for cultures grown on conditioned Biosilicate® surfaces; the exposure of cells to the ionic dissolution products increased Runx2 and ALP mRNA levels. At day 14, significantly more extensive areas of matrix mineralization were detected for cultures grown on Biosilicate® discs that were pre-conditioned with supplemented culture medium. The results showed that the conditioning of Biosilicate® surfaces with culture medium prior to cell plating supports key aspects of cell-substrate interactions, increasing and/or accelerating expression of the osteoblastic cell phenotype. Furthermore, the exposure of cells to the ionic dissolution products of Biosilicate® inhibits the progression of osteogenic cell cultures on bioinert glass coverslips, despite its positive effect on expression of osteoblastic markers.
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Henderson, Samantha [Verfasser], Claus-Henning [Akademischer Betreuer] Köhne, and Jochen [Akademischer Betreuer] Casper. "Treosulfan, Fludarabine and Cytarabine as a Conditioning Regimen for Allogeneic Haematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukaemia, Myelodysplastic Syndrome and Myeloproliferative Neoplasms / Samantha Henderson ; Claus-Henning Köhne, Jochen Casper." Oldenburg : BIS der Universität Oldenburg, 2020. http://d-nb.info/1228535612/34.
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Coracin, Fabio Luiz. "Estudo do polimorfismo C677T do gene da metilenotetrahidrofolato redutase (MTHFR) em pacientes com mucosite de trato gastrointestinal após transplante alogênico de medula óssea." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-11122009-092547/.
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A mucosite oral, também chamada recentemente de mucosite do trato gastrointestinal, continua sendo um importante efeito colateral que pode comprometer o resultado do transplante de células tronco hematopoéticas. Ela pode ocorrer em 100% dos pacientes submetidos ao transplante alogênico de células-tronco e a maior incidência neste pode ser atribuída à administração de metotrexate. A ocorrência de mucosite ulcerativa está relacionada ao aumento dos custos hospitalares, a redução da sobrevida em 100 dias e infecção sistêmica aumentando o risco de sepse. A última década foi muito importante para a compreensão da mucosite oral, incluindo a predisposição genética dos indivíduos e alterações nas enzimas responsáveis a metabolização de quimioterápicos. Recentemente, o polimorfismo C677T no gene metilenotetrahidrofolato redutase (MTHFR) têm ganhado enfoque na relação com a incidência da mucosite. Esta enzima metaboliza o metotrexate e a ela é atribuída maior ou menor atividade levando a modificações na metabolização do fármaco. Poucos trabalhos prospectivos e caso-controle são encontrados na literatura corrente com relação ao polimorfismo C677T e a incidência da mucosite. O objetivo deste estudo foi uma análise prospectiva caso-controle da relação do polimorfismo MTHFR C677T com a incidência da mucosite. Além disso, a influência da condição de saúde bucal (presença de placa dental e inflamação gengival) com a incidência de mucosite oral foi analisada. Foram inseridos 97 pacientes divididos em 2 grupos: 35 pacientes submetidos ao transplante alogênico e 62 pacientes submetidos ao transplante autólogo. A mediana de idade foi de 41,5 anos. O regime de condicionamento consistiu de busulfano e melfalano ou regime BEAM - becenum, etoposide, citarabina e melfalano (para a Doença de Hodgkin e Linfoma não Hodgkin). A profilaxia da doença do enxerto contra o hospedeiro foi feita com ciclosporina e metotrexate, no transplante alogênico. Não foi feito resgate com ácido folínico durante a administração de metotrexato. Os resultados mostraram que o polimorfismo C677T não foi significativo no grupo de estudo em comparação com o grupo controle na previsão de incidência e severidade da mucosite oral. No entanto, a incidência e gravidade da mucosite oral foram influenciadas pela condição de saúde bucal. Em conclusão, o polimorfismo C677T da MTHFR não foi relacionado ao oral mucosite, mas o estado de saúde oral foi um fator importante no desenvolvimento da mucosite. Estes resultados reforçam a importância de um dentista na equipe multiprofissional de assistência a estes pacientes.Oral mucositis remains an important side-effect and life-threatening complication of hematopoietic stem cell transplantation. It can occurs in 100% of patients underwenting allogeneic stem cell transplantation. The differences in incidence between allogeneic and autologous transplantation may be due to methotrexate administration in the first. Ulcerative mucositis is related to increase hospitalar costs, reduced 100-days survival and systemic infections leading to sepsis risk. The last decade was very important to the understanding of oral mucositis, including genetics changes in enzymes responsible to drug metabolization, as the C677T polymorphism in the methylenetethrahidrofolate reductase gene (MTHFR). A prospective evaluation of oral mucositis in relation to the C677T MTHFR polymorphism was done. Also, the influence of oral health condition (presence of dental plaque and gingival inflammation) with the incidence of oral mucositis was analyzed. A cohort of 97 patients (35 allogeneic-study group and 62 autologous-control group) with median age of 41.5 years was evaluated. Conditioning regimen comprised busulfan and melphalan or becenum based conditioning regimen (BEAM becenum, etoposide, cytarabin and melphalan. GVHD prophylaxis comprised cyclosporine A plus short course of methotrexate in allogeneic transplantation. No rescue with folinic acid was done in the methotrexate administration. Results showed that C677T polymorphism was not significant in the study group compared with control group in predicting incidence and severity of oral mucositis. However, the incidence and severity of oral mucositis was influenced by oral health condition. In conclusion, C677T MTHFR polymorphism was not related to oral mucositis, but oral health status was an important factor in developing mucositis. These findings reinforce the importance of a dentist in the multiprofessional team to assist these patients.
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Whalen, Michael. "Treating GM1 Gangliosidosis With Ex Vivo Hematopoietic Stem Cell Gene Therapy Without Using Total Body Irradiation: A Masters Thesis." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/558.
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GM1 gangliosidosis is an autosomal recessive lysosomal storage disease, caused by a deficiency in the enzyme β-galactosidase. The disease affects the CNS, liver, kidney, heart and skeletal system, leading to severe neurodegeneration and death. We propose to treat this disorder using ex vivo hematopoietic stem cell therapy. The effectiveness of this therapy requires the recruitment of transduced donor cells to the CNS. This is only found to occur after mice are conditioned with total body irradiation, due to the increase in CNS cytokine production and blood brain barrier permeability that occurs. As the use of total body irradiation in pediatric patients has been linked to future developmental problems, this myeloablation approach is often avoided in younger patients in favor of a conditioning regimen using the chemotherapy drugs, busulfan and cyclophosphamide. Whether donor cells can enter the CNS when a busulfan and cyclophosphamide conditioning regimen is used has not been determined. In this study we plan to quantify the cytokine and blood-brain barrier permeability increases necessary for donor cells to be recruited to the CNS after total body irradiation. We will then investigate whether busulfan and cyclophosphamide conditioning and/or the chronic neuroinflammation present in GM1 mice can produce similar conditions and facilitate the recruitment of donor hematopoietic stem cells to the CNS. Finally we will assess whether ex vivo hematopoietic stem cell gene therapy is still an effective therapy when busulfan and cyclophosphamide are used for myeloablative conditioning.
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Acosta, Sandra Antonieta. "Multivariate Anti-inflammatory Approaches to Rescue Neurogenesis and Cognitive function in Aged Animals." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3712.
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Studies have shown that there is a strong correlation between aging and neurodegenerative diseases. Aging is considered the number one risk factor to develop neuropathologies such as memory loss, senile dementia, Alzheimer's disease (AD), and Parkinson's disease. Neurodegenerative diseases tend to start during adulthood, and aggravate over time, making them difficult to prevent and to treat. In the Unites States, demographic studies by U.S. Bureau of the Census have determined that our aging population of >65 years is expected to increase from the present 35 million to 78 million in 2030. This would result, not only to an increase of age-related chronic illness, and mental disability, but to a decrease of quality of life, and an elevation of medical cost. Thus, this dissertation has focused on investigating the molecular mechanisms during the process of aging and its correlation to chronic inflammation and cognitive impairments. The etiology of neurodegenerative diseases is not very well understood, but research has shown that the process of aging is a key factor, which involved oxidative stress, an over reactive microglia, and increased production of pro-inflammatory cytokines. All these factors are known to decrease cell proliferation, which limit neuroplasticity and they might lead the transition from normal aging to more severe cognitive dysfunction associated with neurodegenerative diseases. Previously, we have shown that natural compounds such as polyphenols from blueberry, and green tea, and amino acids like carnosine are high in antioxidant and anti-inflammatory activity that decreases the damaging effects of reactive oxygen species (ROS), in the blood, brain, and other tissues of the body. Therefore, we examined the hypothesis that the pro-inflammatory cytokine TNF-[U+F061] may be a critical factor that modulates classical conditioning behavior, the effects of NT-020 on adult neurogenesis, inflammatory markers of the CNS, and the effect of NT-020 on cognitive function as shown using spatial navigation task. The results show that in aged rats, endogenous production of pro-inflammatory cytokine TNF-α impairs the acquisition of learning and memory consolidation in the delay eyeblink classical conditioning task (EBC). It was shown that this effect can be replicated by infusing young rats with exogenous TNF-α prior to EBC. Using NT-020 as a dietary supplement for one month, it was found that NT-020 ameliorates the age-related impairments typically found in aged rats in the spatial navigation tasks Morris water maze and radial arm water maze. By looking at immunohistochemistry analysis, it was found a decreased number of OX6 MHC II positive cells, increased neurogenesis, and increased number of proliferating cells in the dentate gyrus (DG) of the hippocampus in the aged rats fed with NT-020 relative with their counterpart aged control. In the CNS, Inflammatory markers were analyzed, and it was found that aged rat fed with NT-020 supplemented diet has decrease levels of pro-inflammatory cytokines in compared with aged rats fed with NIH-31 control diet. In conclusion, TNF-α, a pro-inflammatory cytokine has shown to have a modulatory effect during classical conditioning. Moreover, NT-020 may promote a healthy CNS milieu, proliferation of neuronal progenitors, and maintenance of nature neurons in the aged rats and it might exert anti-inflammatory actions which promote a functional stem cell pool in the CNS of aged rats.
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Forman, Daron. "Viral Abrogation of Stem Cell Transplantation Tolerance Causes Graft Rejection and Host Death by Different Mechanisms: A Dissertation." eScholarship@UMMS, 2002. https://escholarship.umassmed.edu/gsbs_diss/72.
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Tolerance-based stem cell transplantation using sub-lethal conditioning is being considered for the treatment of human disease, but safety and efficacy remain to be established. In order to study these two issues, we first established that mouse bone marrow recipients treated with sub-lethal irradiation plus transient blockade of the CD40-CD154 costimulatory pathway develop permanent hematopoietic chimerism across allogeneic barriers. Our conditioning regimen of 6 Gy irradiation, a short course of anti-CD154 mAb and 25 million fully allogeneic BALB/c bone marrow cells consistently produced long-term, stable, and multilineage chimerism in C57BL/6 recipients. Furthermore, chimeric mice displayed donor-specific transplantation tolerance, as BALB/c skin allografts were permanently accepted while third-party CBA/JCr skin allografts were promptly rejected. We next determined both the safety and efficacy of this protocol by infecting chimeric mice with lymphocytic choriomeningitis virus (LCMV) either at the time of transplantation or at several time points afterwards. Infection with LCMV at the time of transplantation prevented engraftment of allogeneic, but not syngeneic, bone marrow in similarly treated mice. Surprisingly, infected allograft recipients also failed to clear the virus and died. Post-mortem study revealed hypoplastic bone marrow and spleens. Hypoplasia and death in these mice required the combination of 6 Gy irradiation, LCMV infection on the day of transplantation, and an allogeneic bone marrow transplant but did not require the presence of anti-CDl54 mAb. Allochimeric mice infected with LCMV 15 days after transplantation were able to survive and maintain their bone marrow graft, indicating that the deleterious effects of LCMV infection on host and graft survival are confined to a narrow window of time during the tolerization and transplantation process. The final section of this thesis studied the mechanisms of graft rejection and death in sublethally irradiated recipients of allogeneic bone marrow and infection with LCMV at the time of bone marrow transplantation. Infection of interferon-α/β receptor knockout mice at the time of transplantation prevented the engraftment of allogeneic bone marrow, but the mice survived. Therefore, IFN-αβ is involved in the development of marrow hypoplasia and death, whereas a second mechanism is involved in blocking the development of chimerism in these mice. Through the use of depleting mAb's and knockout mice we demonstrate that three types of recipients survived and became chimeric after being given sublethal irradiation, anti-CD154 mAb, an allogeneic bone marrow transplant and a day 0 LCMV infection: mice depleted of CD8+ T cells, CD8 knockout mice, and TCR-αβ knockout mice. Our data indicate that the mediator of bone marrow allograft destruction in LCMV-infected mice treated with costimulatory blockade is a radioresistant CD8+ NK1.1- TCRαβ+ T cell. We conclude that a non-cytopathic viral infection at the time of transplantation can prevent engraftment of allogeneic bone marrow and result in the death of sub-lethally irradiated mice treated with costimulation blockade. The abrogation of allogeneic bone marrow engraftment is mediated by a population of CD8+ NK1.1- TCRαβ+ T cells and the mediator of hypoplasia and death is viral induction of IFN-αβ.
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Santos, Kelli Borges dos. "Efetividade e toxicidade de protocolo de condicionamento em transplante autólogo de célula-tronco hematopoética para pacientes com linfoma." Universidade Federal de Juiz de Fora, 2015. https://repositorio.ufjf.br/jspui/handle/ufjf/1288.
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Introdução: Nas últimas décadas, o transplante autólogo de células-tronco hematopoéticas (auto-TCTH) tem sido utilizado como uma potencial terapia de salvamento para pacientes portadores de linfomas. Atualmente, inúmeros tipos de protocolos de condicionamento para a realização do auto-TCTH são conhecidos e utilizados com a intenção de melhorar a sobrevida global (SG) e livre de doença (SLD) destes pacientes. Até os dias atuais, nenhum protocolo tem sido considerado superior, com melhores resultados que os outros. Objetivo: Determinar a dose máxima de lomustina tolerada em protocolo de condicionamento (lomustina, etoposide, citarabina e melfalan – LEAM) e avaliar as toxicidades deste protocolo em comparação a série histórica do serviço. Método: Trata-se de uma coorte prospectiva, do tipo 3:3, quantitativa. A primeira etapa do estudo foi realizada para a determinação da dose máxima tolerada (DMT) de lomustina. A segunda etapa, consistiu na comparação com a série histórica de pacientes submetidos ao transplante que utilizaram CBV (carmustina, etoposide e ciclofosfamida) previamente ao auto-TCTH. Resultados: Para determinar a dose máxima tolerada (DMT) de lomustina administrada no D-4, seguida de etoposide (1 g/m2 D-3), citarabina (4g/m2 D-2), e melfalano (140 mg/m2 D-1), foram submetidos ao protocolo um total de 14 pacientes. Foi realizado escalonamento da dose de lomustina a cada 200 mg/m2. A coorte inicial consistiu de lomustina na dose de 200 mg/m2 (L200), seguida de uma coorte com lomustina 400 mg/m2 (L400). Como L400 excedeu a DMT, uma terceira coorte foi criada com lomustina 300 mg/m2 (L300). Seis pacientes foram tratados em L200 (1 Toxicidade Limitante de Dose (TLD) – óbito por sepse), dois pacientes foram tratados em L400 (2 TLD, toxicidade gastrointestinal grau 4) e 6 pacientes foram tratados em L300 (1 TLD, neurológica grau 4, reversível), sendo lomustina 300mg/m2 considerada a DMT. Na segunda fase do estudo participaram 32 pacientes submetidos ao protocolo LEAM. As principais toxicidades encontradas entre os pacientes foram mucosite (53,1%), diarreia (68,8%) e toxicidade cutânea (34,4%). A seguir, os pacientes foram comparados a séria histórica, em que 64 pacientes foram submetidos ao protocolo CBV. Os grupos eram similares no que diz respeito ao estádio, diagnóstico médico idade e sexo. O início da neutropenia e o tempo de duração da mesma foi estatisticamente menor no grupo LEAM em comparação ao grupo CBV, p = 0,00 e 0,035 respectivamente. Não houve diferença entre as toxicidades encontradas nos dois grupos, no entanto, a sobrevida global dos pacientes submetidos ao protocolo LEAM foi superior em comparação ao grupo CBV (p = 0,050). Conclusão: O protocolo LEAM mostrou-se como um regime de condicionamento factível, de rápida administração, associado a curto período de neutropenia e aceitável toxicidade. A sobrevida global foi melhor no protocolo LEAM quando comparada a série histórica do serviço.
Introduction: In recent decades, Autologous Hematopoietic Stem Cell Transplantation (auto-HSCT) has been used as a potential rescue therapy for patients with lymphoma. Currently, numerous types of conditioning protocols for performing auto-HSCT are known and used in order to improve the overall survival (OS) and disease-free survival (DFS) of these patients. Until today, no protocol has been considered superior and produced better results than the others. Objective: Determine the maximum tolerated dose of lomustine in a conditioning protocol (lomustine, etoposide, cytarabine and melphalan – LEAM) and evaluate the toxicities of this protocol in comparison to the historical series of the service. Method: A quantitative, type 3.3 prospective cohort. The first step of the study was carried out to determine the maximum tolerated dose (MTD) of lomustine. The second step consisted in comparing it with the historical series of patients undergoing transplantation who used CBV (carmustine, etoposide and cyclophosphamide) prior to auto-HSCT. Results: To determine the maximum tolerated dose (MTD) of lomustine administered on D-4, followed by etoposide (1 g/m2 (D-3), cytarabine (4 g/m2 (D-2), and melphalan (140 mg/m2 (D-1), a total of 14 patients were submitted to the protocol. The lomustine dose was escalated according to 200 mg/m2 intervals. The initial cohort consisted of lomustine at a dose of 200 mg/m2 (L200), followed by a cohort with lomustine 400 mg/m2 (L400). Because L400 exceeded the MTD, a third cohort with lomustine in a dose of 300 mg/m2 was created (L300). Six patients were treated in L200 (1 DLT, died of sepsis), two patients were treated in L400 (2 DLT, grade 4 gastrointestinal toxicity) and 6 patients were treated in L300 (1 DLT, neurological grade 4, reversible), with lomustine 300mg/m2 being considered the MTD. In the second phase of the study, 32 patients submitted to the LEAM protocol participated. The main toxicities found among the patients were mucositis (53.1%), diarrhea (68.8 %) and dermal toxicity (34.4%). The patients were then compared to the historical series, in which 64 patients were submitted to the CBV protocol. The groups were similar with regard to the stage, medical diagnosis, age and sex. The beginning of neutropenia and its duration was statistically lower in the LEAM group when compared to the CBV group, p = 0.00 and 0.035, respectively. There was no difference between the toxicities found in the two groups, but the overall survival of the patients submitted to the LEAM protocol was higher when compared to the CBV group (p = 0.050). Conclusion: The LEAM protocol proved to be a viable conditioning regimen of rapid administration, associated with a short duration of neutropenia and acceptable toxicity. Overall survival was better in the LEAM protocol when compared to the historical series of the service.
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Goh, Wil. "Conditioning murine B cells for immunoglobulin A production In vitro." Thesis, Goh, Wil (2012) Conditioning murine B cells for immunoglobulin A production In vitro. Honours thesis, Murdoch University, 2012. https://researchrepository.murdoch.edu.au/id/eprint/11830/.
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The respiratory mucosa is continuously exposed to a myriad of pathogens and allergens that are inhaled during respiration. B cells of the immune system produce immunoglobulin A (IgA) that protects the respiratory mucosa from inhaled pathogens and allergens. IgA is produced after naïve B cells undergo activation, proliferation and differentiation, developing into antibody producing plasma cells. The process that facilitates IgA production as B cells develop into plasma cells is known as class switch recombination (CSR).
Factors favouring IgA have been determined by in vitro studies of CSR. These established two cytokines, IL-21 and TGF-β1, to be important factors for IgA production. Prior studies with human naïve B cells that were cultured with IL-21 and TGF-β1, in addition to anti-IgM, anti-CD40, IL-2 and CpG, developed into precursors of IgA producing plasma cells (plasmablasts) that possessed mucosal homing capabilities: a process termed B cell conditioning.
The aim of this project was to establish whether the same factors were active on murine naïve B cells in order to eventually test the in vivo therapeutic potential of B cell conditioning. A protocol was optimised for CD19+CD27- naïve B cell isolation from mouse spleen and cell division, which is crucial for IgA CSR, by CFSE labelling and flow cytometry. The number of divisions predicts the generation of IgA mucosal homing plasmablasts in vitro. Cells were found to have undergone 5 divisions after 7 days in culture suggesting that cells had undergone a sufficient number of divisions for CSR and IgA production. Attempts were made to quantitate IgA production in culture supernatants, however evidence for the generation of these cells by IgA production remains to be confirmed. The results of this project provide preliminary evidence that murine naïve B cells can be conditioned in vitro for IgA production, with potential for homing to, and protection of, mucosal surfaces in vivo.
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Bockhart, James David. "Conditioning 3D biomimetic scaffolds for the cultivation of transplantable beta cells." Thesis, University of Brighton, 2013. https://research.brighton.ac.uk/en/studentTheses/06e474c1-fbd9-49d7-89ef-55c4e571ee42.
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Islet transplantation holds vast potential as a treatment for type 1 diabetes mellitus and provides recipients with short term insulin independence. A major limitation of this treatment is the lack of donor beta (β) cells available for transplantation. Significant progress has been made with stem cell differentiation protocols; current methods have generated cell populations which possess a functioning β cell phenotype. However, these cells are not suitable for clinical transplantation. Two dimensional cell culture systems do not accurately mimic the complexity of the in vivo pancreatic environment, reducing the effectiveness of current β-cell differentiation protocols. The paradigm shift into three dimensional tissue culture provides an attractive area of investigation, and the use of three dimensional culture methods has improved growth in a variety of cell types ex vivo. The mass culture of β cell analogues on a 3D biomimetic environment is now necessary, and may offer a new platform on which an alternative source of transplantable cell populations can be differentiated and cultured successfully. This thesis aims to develop and condition BioVyon™, a high density polyethylene (HDPE) based biomaterial, for use as a mass β cell cultivation system In order to achieve this, a number of objectives will need to be met: (I) Complete characterisation and assessment of all properties of Biovyon™ that have a direct influence on cell culture, (ii) modification of the BioVyon™ surface chemistry to promote cell adhesion and growth, (iii) absorbance of proteins to mimic the pancreatic environment and aid proliferation of the Min-6 cell line, (iv) assessment of the Min-6 cell line phenotype after extended period of culture on the modified BioVyon ™ environment. Scanning electron microscopy and Atomic Force Microscopy were used to characterise the surface of the HDPE material post plasma etching. Advancing and receding (ARCA) and Fourier Transform Infrared Spectroscopy were used to analyse the elemental changes to the polymer surface. The HDPE biomaterial was conditioned using plasma etching, subsequent adhesion and growth of Min-6 cells was quantified using a lactate dehydrogenase assay. Min-6 populations were seeded at a density of lxl0/6i on BioVyon™ and tissue culture plastic of comparable surface area, and analysed after extended periods of growth. An insulin EUSA was used to quantify insulin released by populations of β cells at different time points witin the BioVyon™ in response to fluctuating glucose concentrations. The results obtained in this thesis indicate that BioVyon™ offers an appropriate structural environment for cell culture. Pore size and frit dimensions allow for cell infiltration and the effective diffusion of oxygen and nutrients. Plasma etching incorporated oxygen groups and a novel surface topography that improved cell adhesion and growth. β-cell phenotype was protected and sustained in cell populations cultured within the BioVyon™ environment. In conclusion, BioVyon™ can be conditioned to function as an effective 30 cell culture system. Modification of the surface chemistry has enabled BioVyonTl • to harbour and sustain large populations of the Min-6 cell line. The protected β-cell phenotype in the Min-6 populations suggests BioVyon™ could hold potential as a stem cell culture and differentiation platform.
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Hofmann, Marc. "Rear surface conditioning and passivation for locally contacted crystalline silicon solar cells." München Verl. Dr. Hut, 2008. http://d-nb.info/992163250/04.
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To, Kar-wing. "Molecular modifications and functional conditioning of dendritic cells (DC) for DC-based tumor vaccines." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38860144.
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To, Kar-wing, and 杜嘉詠. "Molecular modifications and functional conditioning of dendritic cells(DC) for DC-based tumor vaccines." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38860144.
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Koran, Ahmed Mohammed. "Photovoltaic Source Simulators for Solar Power Conditioning Systems: Design Optimization, Modeling, and Control." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/23681.
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This dissertation presents various systematic design techniques for photovoltaic (PV) source simulators to serve as a convenient tool for the dynamic performance evaluation of solar power conditioning systems and their maximum power point tracking algorithms. A well-designed PV source simulator should accurately emulate the static and the dynamic characteristic of actual PV generator. Four major design features should be adopted in any PV source simulator: (i) high power-stage efficiency, (ii) fast transient response-time, (iii) output impedance matching with actual PV generator, and (iv) precise reference generation technique. Throughout this research, two different PV source simulator systems are designed, modeled, and experimentally verified. The design of the first system focuses mainly on creating new reference generation techniques where the PV equivalent circuit is used to precisely generate the current-voltage reference curves. A novel technique is proposed and implemented with analog components to simplify the reference signal generator and to avoid computation time delays in digital controllers. A two-stage LC output filter is implemented with the switching power-stage to push the resonant frequency higher and thus allowing a higher control-loop bandwidth design while keeping the same switching ripple attenuation as in the conventional one-stage LC output filter. With typical control techniques, the output impedance of the proposed simulator did not match the closed-loop output impedance of actual PV generator due to the double resonant peaks of the two-stage LC output filter. Design procedures for both control and power-stage circuits are explained. Experimental results verify the steady-state and transient performance of the proposed PV source simulator at around 2.7 kW output.
The design concept of the first simulator system is enhanced with a new type of PV source simulator that incorporates the advantages of both analog and digital based simulators. This simulator is characterized with high power-stage efficiency and fast transient response-time. The proposed system includes a novel three-phase ac-dc dual boost rectifier cascaded with a three-phase dc-dc interleaved buck converter. The selected power-stage topology is highly reliable and efficient. Moreover, the multi-phase dc-dc converter helps improve system transient response-time though producing low output ripple, which makes it adequate for PV source simulators.
The simulator circuitry emulates precisely the static and the dynamic characteristic of actual PV generator under different environmental conditions including different irradiance and temperature levels. Additionally, the system allows for the creation of the partial shading effect on PV characteristic. This dissertation investigates the dynamic performance of commercial and non-commercial solar power conditioning systems using the proposed simulator in steady-state and transient conditions. Closed-loop output impedance of the proposed simulator is verified at different operating conditions. The impedance profile --magnitude and phase- matches the output impedance of actual PV generator closely. Mathematical modeling and experimental validation of the proposed system is thoroughly presented based on a 2.0 kW hardware prototype. The proposed simulator efficiency including the active-front-end rectifier and the converter stages at the maximum power point is 96.4%.
Ph. D.
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CORRADETTI, VALERIA. "Pre-transplant conditioning of isolated rat kidney by perfusion with mesenchymal stromal cells/extracellular vesicles prevents ischaemic injury." Doctoral thesis, Università degli studi di Pavia, 2018. http://hdl.handle.net/11571/1227788.
Full textAbstract:
IL CONDIZIONAMENTO DI UN RENE DI RATTO PRIMA DEL TRAPIANTO CON CELLULE MESENCHIMALI STROMALI E/O CON MICROVESCICOLE PREVIENE IL DANNO DA ISCHEMIAKidney donation after circulatory death (DCD) is a less than ideal option to meet organ shortages. Hypothermic machine perfusion (HMP) with Belzer solution (BS) improves the viability of DCD kidneys, although the graft clinical course remains critical. Mesenchymal stromal cells (MSC) promote tissue repair by releasing extracellular vesicles (EV). We evaluated whether delivering MSC-/MSC-derived EV during HMP protects rat DCD kidneys from ischaemic injury and investigated the underlying pathogenic mechanisms. Warm ischaemic isolated kidneys were cold-perfused (4 hrs) with BS, BS supplemented with MSC or EV. Renal damage was evaluated by histology and renal gene expression by microarray analysis, RT-PCR. Malondialdehyde, lactate, LDH, glucose and pyruvate were measured in the effluent fluid. MSC-/EV-treated kidneys showed significantly less global ischaemic damage. In the MSC/EV groups, there was up-regulation of three genes encoding enzymes known to improve cell energy metabolism and three genes encoding proteins involved in ion membrane transport. In the effluent fluid, lactate, LDH, MDA and glucose were significantly lower and pyruvate higher in MSC/EV kidneys as compared with BS, suggesting the larger use of energy substrates by MSC/EV kidneys. The addition of MSC/EV to BS during HMP protects the kidney from ischaemic injury by preserving the enzymatic machinery essential for cell viability and protects the kidney from reperfusion damage.
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Amirrasouli, Muhammad Mehdi. "Characterisation of cardiosphere derived cells : investigating hypoxic pre-conditioning on pro-angiogenic properties and tracking the cardiac fibroblast component." Thesis, University of Newcastle upon Tyne, 2014. http://hdl.handle.net/10443/2570.
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Coronary heart disease is still the leading cause of death in the UK, despite significant advances in clinical treatments. Stem cell transplantation has the potential to improve cardiac function and patient outcome, but optimal cell types, cell preparation methods and cell delivery routes are yet to be established. The heart contains a small population of progenitor cells that, in culture, contribute to spontaneously formed spheroids known as cardiospheres (Csphs). Following further culture, Csphs give rise to cardiosphere derived cells (CDCs). Both Csphs and CDCs show paracrine benefit including neovascularisation in myocardial ischaemia, leading to improvement in heart function. The aims of this project were to use mouse models to (i) investigate the effect of hypoxic preconditioning on the pro-angiogenic potential of CDCs and (ii) characterise the contribution of cardiac fibroblasts (CFs) to CDCs. I used Col1a2-CreERT;Rosa26-STOP-YFP mice to track YFP-expressing CFs in myocardial tissue and in CDC culture. Co-staining experiments showed only partial overlap of YFP with other CF markers (vimentin and Fsp1) in heart tissue, which may be due to the heterogeneity of CFs and/or incomplete activation of YFP in CFs. I showed that CF-derived cells exist in all stages of CDC culture, and a small subset of these cells also expressed the stem cell markers Sca-1 or cKit, suggesting CF derived cells may contribute to the progenitor cell population. My results showed that preconditioning CDCs with 3%O2 enhances cell outgrowth from heart explants and promotes expression of stem cell and pro-angiogenic markers. I then assessed the pro-angiogenic potential of CDCs in vivo using a sub-dermal matrigel plug assay and showed that CDCs alone have limited pro-angiogenic potential. However, 3%O2 preconditioning of CDCs significantly enhances this process. Further research will increase our understanding of CDC-mediated angiogenesis and improve clinical therapies for MI patients.
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Seung, Edward. "CD40-CD154 Blockade Facilitates Induction of Allogeneic Hematopoietic Chimerism and Transplantation Tolerance: A Dissertation." eScholarship@UMMS, 2003. https://escholarship.umassmed.edu/gsbs_diss/103.
Full textAbstract:
Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Establishment of hematopoietic chimerism created by stem cell transplantation has been shown to prevent and cure a number of autoimmune diseases and induce the most robust and long-lasting form of transplantation tolerance known. However, the realization of the vast clinical potential of hematopoietic chimerism for induction of transplantation tolerance has been impeded by the toxicity of the host conditioning regimen and the development of graft-versus-host disease (GVHD). This thesis describes the development of stem cell transplantation protocols that 1) reduce the host conditioning regimen; and 2) abrogate the development of GVHD. When applied to the treatment of autoimmune diabetic NOD mice, a model of type 1 diabetes, stem cell transplantation was able to 3) prevent autoimmune recurrence; and 4) permit curative pancreatic islet transplantation.
I first describe a tolerance-based stem cell transplantation protocol that combines sub-lethal irradiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With this protocol, I established hematopoietic chimerism in BALB/c mice transplanted with fully allogeneic C57BL/6 bone marrow. All chimeric mice treated with anti-CD154 antibody remained free of graft vs.host disease (GVHD) and accepted donor-origin but not third party skin allografts. It was similarly possible to create allogeneic hematopoietic chimerism in NOD/Lt mice with spontaneous autoimmune diabetes. Pancreatic islet allografts transplanted into chimeric NOD/Lt mice were resistant not only to allorejection but also to recurrence of autoimmunity. I conclude that it is possible to establish robust allogeneic hematopoietic chimerism in sub-lethally irradiated mice without subsequent GVHD by blocking the CD40-CD154 costimulatory pathway using as few as two injections of anti-CD154 antibody. I also conclude that chimerism created in this way generates donor-specific allograft tolerance and reverses the predisposition to recurrent autoimmune diabetes in NOD/Lt mice, enabling them to accept curative islet allografts.
In order to further reduce the impediments associated with the implementation of allogeneic hematopoietic chimerism as a therapeutic modality, I adapted a costimulation blockade-based protocol developed for solid organ transplantation for use in stem cell transplantation. The protocol combines a donor-specific transfusion (DST) with anti-CD154 antibody to induce peripheral transplantation tolerance. When applied to stem cell transplantation, administration of DST, anti-CD154 antibody, and allogeneic bone marrow led to hematopoietic chimerism and central tolerance with no myeloablation (i.e. no radiation) and no GVHD in 3 different strains of mice. The development of donor-specific tolerance in this system was shown to involve deletion of both peripheral host alloreactive CD8+ T cells and nascent intrathymic alloreactive CD8+ T cells. In the absence of large numbers of host alloreactive CD8+ T cells, the cell transfusion that precedes transplantation need not be of donor-origin, suggesting that both allo-specific and non-allo-specific mechanisms regulate engraftment. Agents that interfere with peripheral transplantation tolerance partially impair establishment of chimerism. I conclude that robust allogeneic hematopoietic chimerism and central tolerance can be established in the absence of host myeloablative conditioning using a peripheral transplantation tolerance protocol.
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Llucià, Valldeperas Aida. "Physiological conditioning of adult progenitor cells boosts cardiac regeneration = El condicionament fisiològic de cèl·lules progenitores adultes promou la regeneració cardíaca." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/396333.
Full textAbstract:
The optimal cell lineage for cardiac regeneration remains elusive; and current treatments, with the exception of heart transplantation, are not enough to restore myocardial function. Thus, new strategies, such as cardiac tissue engineering, are now emerging as a new therapeutic modality. On the other hand, cardiac cells are normally subjected to electrical and mechanical forces that regulate gene expression and cellular function.
Therefore, our hypothesis claims that in vitro individual or combined synchronous electro-mechanical stimuli mimicking the cardiac environment, could mature or induce cardiac differentiation on therapeutic cells to benefit further retention and integration into the myocardium.
This thesis proposal had several goals:
1. Design an ad-hoc device to supply electrical and mechanical stimuli, individually or synchronously, to a monolayer cell culture.
2. Design a protocol for electrical, mechanical and electromechanical conditioning.
3. Analyze the cardiomyogenic effect of electrical, mechanical and electromechanical conditioning on adipose tissue-derived progenitor cells (ATDPCs) and cardiomyocyte progenitor cells (CMPCs).
4. Study the feasibility of a tissue engineered construct with trained cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs).
5. Examine the regenerative capacity of electromechanically conditioned cardiac ATDPCs within a myocardial infarction murine model.
Summing up, the conclusions derived from this thesis project are:
1. A new device for ad-hoc electrical and mechanical stimulation, individually or synchronously, has been developed in collaboration with the Electronic and Biomedical Instrumentation Group from the Universitat Politècnica de Barcelona. This device has been patented (WO 2013185818 A1) including some results obtained in this thesis.
2. Protocols for electrical, mechanical and electromechanical conditioning on cardiac ATDPCs culture were designed and optimized with the aim to mimic the cardiac environment.
3. Electrical stimulation on cardiac ATDPCs and CMPCs enhances the expression of cardiac transcription factors (MEF2A and GATA-4) crucial for cardiac differentiation. In addition, electrical conditioning promotes cardiac ATDPCs elongation and cell alignment.
4. Mechanical stimulation on cardiac ATDPCs upregulates cardiac transcription factors (GATA-4 and Tbx5) and structural genes (α-actinin and cTnI) expression, strongly dependent on the patterned surface.
5. In vitro electro-mechanical stimulation pre-commits the cell population against the hostile cardiac milieu through increased expression of cardiac transcription factors (Tbx5 and GATA-4), structural genes (b-MyHC) and, most importantly, calcium handling genes (Cx43 and SERCA2).
6. Conditioned cardiac ATDPCs fibrin constructs scarcely migrate to the murine myocardium, de novo express cTnI in vivo, increase vessel density and promote the sprouting of functional blood vessels, and improve cardiac function with only 105 implanted cells.El llinatge cel·lular òptim per a la regeneració cardíaca continua sent un gran desconegut. Els tractaments actuals són insuficients per a restablir la funció cardíaca, exceptuant el trasplantament de cor. Per això, noves estratègies, com l’enginyeria tissular cardíaca, estan emergent com a noves modalitats terapèutiques. D’altra banda, les cèl·lules cardíaques estan normalment subjectes a estímuls elèctrics i mecànics, que regulen la seva expressió gènica i la funció cel·lular. Per tant, la hipòtesi d’aquest treball és que el pre-condicionament in vitro, mitjançant estímuls biofísics similars a l’entorn cardíac, podria madurar i induir cert grau de diferenciaicó cardíaca a les cèl·lules terapèutiques. Així es milloraria la seva retenció i integració al miocardi hoste, i beneficiaria el tractament de l’infart de miocardi. Els objectius d’aquest treball són: 1. Disseny i producció d’un aparell apte per a portar a terme el condicionament elèctric i mecànica, individualment o de manera combinada, a un cultiu cel·lular en monocapa de cèl·lules progenitores derivades de teixit adipós cardíac (ATDPCs cardíaques). 2. Disseny d’un protocol per al condicionament elèctric, mecànic i electromecànic. 3. Caracterització de les cèl·lules obtingudes de cadascun dels condicionaments. 4. Estudi de la viabilitat d’un constructe d’enginyeria amb ATDPCs cardíaques condicionades. 5. Examinar l’efecte del condicionament electromecànic de les ATDPCs cardíaques implantades, mitjançant un constructe tridimensional, en el model murí d’infart de miocardi. Les conclusions obtingudes són: 1. S’ha desenvolupat un aparell apte per a l’estimulació elèctrica i mecànica, individual o sincrònicament, en col·laboració amb el Grup d’Instrumentació Electrònica i Biomèdica de la Universitat Politècnica de Catalunya. Aquest aparell s’ha patentat (WO 2013185818 A1) amb alguns dels resultats derivats d’aquesta tesi. 2. S’ha dissenyat i optimitzat un protocol per al condicionament elèctric, mecànic i electromecànic de les ATDPCs cardíaques amb la intenció de mimetitzar l’ambient cardíac. 3. L’estimulació elèctrica de les ATDPCs cardíaques i les CMPCs millora l’expressió de factors de transcripció (MEF2A i GATA-4) crucials per a la diferenciació cardíaca. A més, el condicionament elèctric de les ATDPCs cardíaques promou la seva elongació i alineament acord al patró de la superfície. 4. L’estimulació mecànica de les ATDPCs cardíaques incrementa l’expressió genètica de factors de transcripció (GATA-4 i Tbx5) i gens estructurals (α-actinin i cTnI), i és fortament dependent del patró de la superfície. 5. L’estimulació electromecànica in vitro prepara les ATDPCs cardíaques per a l’hostil entorn cardíac augmentant l’expressió de factors de transcripció cardíacs (Tbx5 i GATA-4), gens estructurals (β-MyHC) i gens relacionats amb el maneig del calci (Cx43 i SERCA2). 6. El pegat de fibrina amb ATDPCs cardíaques electromecànicament entrenades promou una escassa migració al miocardi murí, una lleu expressió proteica de cTnI, l’increment de la densitat vascular a la vora de la cicatriu de l’infart, la formació de vasos sanguinis funcionals al miocardi i al constructe, i una millora de la funció cardíaca del 8% amb només 105 cèl·lules.
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Elsaadany, Mostafa. "Modulating Stem Cells Fate and Conditioning the Matrix of 3D in vitro Models using Equiaxial Mechanical Strain towards Annulus Fibrosus Regeneration." University of Toledo / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1498832209192755.
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Barban, Alessandra. "Análise da mobilização e resultados do transplante de células-tronco hematopoiéticas autogênico (TCTHa) com alta hospitalar precoce nos portadores de doenças hematológicas." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-09102013-155104/.
Full textAbstract:
padrão utilizado para algumas doenças hematológicas e também na consolidação do tratamento de outras doenças. O aumento da demanda de pacientes que necessitam deste tratamento fez com que fossem criados alguns modelos de transplante ambulatorial. A alta precoce é uma modalidade de transplante em que o paciente recebe alta hospitalar após o regime de condicionamento e infusão das células-tronco hematopoiéticas (CTH) e a continuidade do seu tratamento ocorre em regime ambulatorial. Na área da Enfermagem, o número limitado de estudos científicos relacionados à Assistência de Enfermagem nos pacientes submetidos ao TCTH com alta hospitalar precoce são ainda deficientes. Diante disso, o objetivo deste estudo foi analisar os resultados da alta hospitalar precoce como alternativa viável ao tratamento dos pacientes submetidos ao TCTHa e sua relação com a assistência de enfermagem. MÉTODO: Estudo retrospectivo, quantitativo, descritivo e transversal. Foram analisados prontuários de 112 pacientes consecutivos submetidos ao TCTHa, no período de janeiro a dezembro de 2009. Destes 12 pacientes não receberam alta hospitalar da unidade de internação até o décimo dia após o TCTH (D+10) e, por isso, foram excluídos, restando 100 pacientes. RESULTADOS: A mediana de idade foi de 48,5 anos (19-69 anos). Houve um pareamento não intencional do sexo. Todos os pacientes mobilizaram e coletaram CTH por fonte periférica. Os regimes de condicionamento mais utilizados foram BU12+Mel100 e BEAM 400. As toxicidades atribuídas ao regime de condicionamento foram bem conduzidas no ambulatório, expressa por 10 pacientes que necessitaram de internação, embora um grande número de pacientes da casuística apresentou algum grau de toxicidade. A neutropenia febril esteve presente em 58% dos pacientes até a enxertia medular. Não houve aumento na mortalidade na fase de aplasia medular; dois pacientes foram a óbito por causas infecciosas durante os 60 primeiros dias após o TCTH, sendo que apenas um não apresentava enxertia medular. A mediana de enxertia de granulócitos após o TCTHa com alta hospitalar precoce foi de 12 dias e de plaquetas 15 dias, com mediana de transfusões até a alta do serviço de três concentrados de hemácias e quatro concentrados de plaquetas. Vinte e três pacientes necessitaram de internação hospitalar em algum momento desde a alta hospitalar após o transplante até o momento de sua alta. CONCLUSÃO: A equipe de enfermagem apresenta papel fundamental no contexto da alta hospitalar precoce na conduta e manejo dos pacientes. O Enfermeiro participou na orientação e condutas durante a fase de mobilização, transplante e acompanhamento ambulatorial. A mediana de tempo para enxertia medular foi de 12 dias e durante a fase de aplasia os pacientes evoluíram com baixa internação e infecção. Houve baixa incidência de complicações e internações, sendo a toxicidade ao regime de condicionamento a maior causa de internação. As toxicidades ao regime de condicionamento apresentadas foram bem manejadas em regime ambulatorial também pela Equipe de EnfermagemThe autologous hematopoietic stem cell transplantation (HSCTa) is a standard treatment used for some hematological malignancies and also in consolidating the treatment of other diseases. The increased number of patients who need this treatment leads to new models of outpatient transplant. The early discharge is a type of transplant in which the patient is discharged after the conditioning regimen and infusion of hematopoietic stem cells (HSC) and the continuity of your treatment will occur in outpatient settings. Although the models of outpatient HSCT are well defined, there is few studies and publications that demonstrate the actual results of this modality. In the field of nursing, the limited number of scientific studies related to nursing care in HSCT patients with early hospital discharge are even more deficient. Thus, the aim of this study was to analyze the results of early discharge as a viable alternative to the treatment of patients undergoing HSCTa and its relationship to nursing care. Methods: A retrospective, quantitative, descriptive and cross study was performed. A total of 112 patients initially enrolled, 12 were excluded due to the discharged occurred after than tenth day after HSCTa (D +10) and, therefore, 100 patients were enrolled in the study. Results: The median age was 48.5 years (range: 19-69 years). There was an unintentional pairing of sex. All patients were mobilized and collected by HSC peripheral source. The conditioning regimens were used more BU12 + Mel100 and BEAM 400. The conditioning regimen-related toxicities was well at the clinic, expressed by 10 patients who required hospitalization, although a large number of patients in the sample had some degree of toxicity. Febrile neutropenia was observed in 58% of patients until the marrow engraftment. There was no increase in mortality in bone marrow aplasia phase, two patients (2%) died of infectious causes during the first 60 days after HSCTa, and only one patient showed no engraftment. The median granulocyte engraftment after HSCTa with early hospital discharge was 12 days and platelets 15 days, with a median transfusion until discharge from the service three and four units of blood transfused platelet concentrates. Twenty-three patients required hospitalization at some time from hospital discharge after transplantation until the time of his discharge. Conclusion: The nursing team has key role in the context of early hospital discharge in the conduct and management of patients. The nurse participated in the orientation and conduct during the mobilization phase, and outpatient transplant. The median time to engraftment was 12 days and during the aplasia phase of the patients improved, with low infection and hospitalization. There was a low incidence of complications and hospitalizations, and the toxicity conditioning regimen the leading cause of hospitalization. The toxicities presented to the conditioning regimen were well managed on an outpatient basis also for the Nursing Team