Dissertations / Theses on the topic 'Stem cell'
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Falk, Anna. "Stem cells : proliferation, differentiation, migration /." Stockholm, 2005. http://diss.kib.ki.se/2006/91-7140-497-X/.
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Karnsund, Alice, and Elin Samuelsson. "Stem Cell Classification." Thesis, KTH, Skolan för teknikvetenskap (SCI), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-214731.
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Machine learning and neural networks haverecently become hot topics in many research areas. They havealready proved to be useful in the fields of medicine andbiotechnology. In these areas, they can be used to facilitatecomplicated and time consuming analysis processes. Animportant application is image recognition of cells, tumours etc.,which also is the focus of this paper.Our project was to construct both Fully Connected NeuralNetworks and Convolutional Neural Networks with the ability torecognize pictures of muscular stem cells (MuSCs). We wanted toinvestigate if the intensity values in each pixel of the images weresufficient to use as indata for classification.By optimizing the structure of our networks, we obtained goodresults. Using only the pixel values as input, the pictures werecorrectly classified with up to 95.1% accuracy. If the image sizewas added to the indata, the accuracy was as best 97.9 %.The conclusion was that it is sensible and practical to use pixelintensity values as indata to classification programs. Importantrelationships exist and by adding some other easily accessiblecharacteristics, the success rate can be compared to a human’sability to classify these cells.
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Hunter, Susan MacLean. "Stem cell pluripotency." Thesis, Cardiff University, 2008. http://orca.cf.ac.uk/54712/.
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Embryonic stem cells (ES cells) are derived by explantation of the embryonic portion of the pre-implantation embryo into culture. These cells have unique properties which have made them invaluable in study of the function of genes
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Tsai, Filip, and Henrik Hellström. "Stem Cell Classification." Thesis, KTH, Skolan för elektro- och systemteknik (EES), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-200606.
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Samuelsson, Elin, and Alice Karnsund. "Stem Cell Classification." Thesis, KTH, Skolan för teknikvetenskap (SCI), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-210867.
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Machine learning and neural networks have recently become hot topics in many research areas. They have already proved to be useful in the fields of medicine and biotechnology. In these areas, they can be used to facilitate complicated and time consuming analysis processes. An important application is image recognition of cells, tumours etc., which also is the focus of this paper.Our project was to construct both Fully Connected Neural Networks and Convolutional Neural Networks with the ability to recognize pictures of muscular stem cells (MuSCs). We wanted to investigate if the intensity values in each pixel of the images were sufficient to use as indata for classification.By optimizing the structure of our networks, we obtained good results. Using only the pixel values as input, the pictures were correctly classified with up to 95.1% accuracy. If the image size was added to the indata, the accuracy was as best 97.9 %.The conclusion was that it is sensible and practical to use pixel intensity values as indata to classification programs. Important relationships exist and by adding some other easily accessible characteristics, the success rate can be compared to a human’s ability to classify these cells.
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Gilner, Jennifer Bushman Kirby Suzanne Lee. "Enrichment of therapeutic hematopoietic stem cell populations from embryonic stem cells." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1232.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Mar. 26, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Pathology and Laboratory Medicine." Discipline: Pathology and Laboratory Medicine; Department/School: Medicine.
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Sarvi, Sana. "Small cell lung cancer and cancer stem cell-like cells." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9542.
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Small cell lung cancer (SCLC) is a highly aggressive malignancy with extreme mortality and morbidity. Although initially chemo- and radio-sensitive, almost inevitable recurrence and resistance occurs. SCLC patients often present with metastases, making surgery not feasible. Current therapies, rationally designed on underlying pathogenesis, produce in vitro results, however, these have failed to translate into satisfactory clinical outcomes. Recently, research into cancer stem cells (CSCs) has gained momentum and form an attractive target for novel therapies. Based on this concept, CSCs are the cause of neoplastic tissue development that are inherently resistant to chemotherapy, explaining why conventional therapies can shrink the tumour but are unable to eliminate the tumour completely, leading to eventual recurrence. Here I demonstrate that SCLC H345 and H69 cell lines contain a subset of cells expressing CD133, a known CSC marker. CD133+ SCLC sub-population maintained their stem cell-like phenotype over a prolonged period of culture, differentiated in appropriate conditions and expressed the embryonic stem cell marker Oct-4 indicating their stem-like phenotype. Additionally, these cells displayed augmented clonogenic efficacy, were chemoresistant and tumorigenic in vivo, distinct from the CD133- cells. Thus, the SCLC CD133 expressing cells fulfil most criteria of CSClike definition. The molecular mechanisms associated with CD133+ SCLC chemoresistance and growth is unknown. Up-regulated Akt activity, a known promoter of resistance with survival advantage, was observed in CD133+ SCLC cells. Likewise, these cells demonstrated elevated expression of Bcl-2, an anti-apoptotic protein compared to their negative counterpart explaining CD133+ cell chemoresistance phenotype. Additionally, CD133+ cells revealed greater expression of neuropeptide receptors, gastrin releasing peptide (GRP) and V1A receptors compared to the CD133- cells. Addition of exogenous GRP and arginine vasopressin (AVP) to CD133+ SCLC cells promoted their clonogenic growth in semi-solid medium, illustrating for the first time neuropeptide dependent growth of these cells. A novel peptide (peptide-1) was designed based on the known structure of the substance P analogues that have shown benefit in animal models and in early clinical trials. This compound inhibited the growth of SCLC cells in in vitro with improved potency and stability compared to previous analogues and reduced tumorigenicity in vivo. Interestingly, peptide-1 was more effective in CD133+ cells due to increased expression of neuropeptide receptors on these cells. In conclusion, my results show that SCLC cells retain a sub-population of cells that demonstrate CSC-like phenotype. Preferential activation of Akt and Bcl-2 survival pathways and enhanced expression of neuropeptide receptors contribute to CD133+ SCLC chemoresistance and growth. Therefore, it can be proposed that CD133+ cells are the possible cause of SCLC development, treatment resistance and disease recurrence. Despite being chemoresistant, CD133+ cells demonstrated sensitivity to peptide-1. The identification of such new analogue that demonstrates efficacy towards resistant CD133+ SCLC cells is a very exciting step forward in the identification of a potential new therapy for resistant disease.
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Eriksson, Malin. "Manipulating neural stem cells." Stockholm, 2010. http://diss.kib.ki.se/2010/978-91-7409-853-2/.
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Gupta, Gunjan. "Effect of chondrocyte-stem cell interactions on chondrogenesis of mesenchymal stem cells." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p1465607.
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Thesis (M.S.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed August 11, 2009). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 128-134).
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Zhang, Jiao, and 张姣. "Regulation of cell proliferation and modulation of differentiation in human induced pluripotent stem cell-derived mesenchumal stem cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B49617503.
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Functional mesenchymal stem cells (MSCs) derived from human induced pluripotent stem cells (iPSCs) may represent an unlimited cell source with superior therapeutic benefits for tissue regeneration to somatic tissue, such as bone marrow (BM)-derived MSC. In the first part of this project, I investigated whether the differential expression of ion channels in iPSC-MSCs was responsible for their higher proliferation capacity than that of BM-MSCs. The expression of ion channels for K+, Na+, Ca2+ and Cl- currents was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The functional role of these ion channels were then verified by patch clamp experiments to compare the electrophysiological properties of iPSC-MSCs versus BM-MSCs. I detected significant mRNA expression of ion channel genes including KCa1.1, KCa3.1, KCNH1, Kir2.1, SCN9A, CACNA1C and Clcn3 in both human iPSC-MSCs and BM-MSCs; while Kir2.2 and Kir2.3 were only observed in human iPSC-MSCs. Furthermore, I identified five types of currents (BKCa, IKDR, IKir, IKCa and ICl) in iPSC-MSCs, while only four of them (BKCa, IKDR, IKir and IKCa) were observed in BM-MSCs. The rate of cell proliferation was 1.4 fold faster in iPSC-MSCs as compared to BM-MSCs. Interestingly, the proliferation rate of human iPSCMSCs was significantly reduced when inhibiting IKDR with shRNA and hEAG1 channel blockers, 4-AP and astemizole. Though to a lesser extent, the proliferation rate of human BM-MSCs also decreased by IKDR blockage. These results demonstrated that hEAG1 channel plays a crucial role in controlling the proliferation rate of human iPSC-MSCs but to a lesser extent in BM-MSCs.
Next, I examined whether forced expression of a transcription factor- myocardin in iPSC-MSC using viral vectors (adenovirus or lentivirus) can further enhance their trans-differentiation to cardiomyocytes and improve their electrophysiological properties for cardiac regeneration. My results on RT-PCR and immunofluorescent staining revealed that myocardin induced the expression of several cardiac and smooth muscle cell markers, including α-MHC, cTnT, GATA4, α-actinin, and cardiac MHC, smooth muscle cell markers MYH11, calponin, and SM α-actin, but not the more mature cardiac markers such as β-MHC and MLC2v in iPSC-MSCs. These findings indicate that forced expression of myocardin in iPSC-MSC resulted in partial trans-differentiation into cardiomyocytes phenotype. Furthermore, I also discovered that myocardin altered the electrophysiological properties of iPSC-MSCs when examined by RT-PCR and patch clamp experiments. Forced expression of myocardin in iPSC-MSC enhanced the expression of Kv4.3, SCN9A and CACNA1C, but reduced that of KCa3.1 and Kir 2.2 in iPSC-MSCs. Moreover, BKCa, IKir, ICl, Ito and INa.TTX were detected in iPSC-MSC with ectopic expression of myocardin; while only BKCa, IKir, ICl, IKDR and IKCa were noted in iPSC-MSC transfected with green florescence protein. Furthermore, as measured by multi-electrode arrays recording plate, the conduction velocity of the neonatal rat ventricular cardiomyocytes cocultured iPSC-MSC monolayer was significantly increased after ectopic expression of myocardin. Taken together, I have demonstrated that hEAG1 channel is important in the regulation of iPSC-MSC proliferation and forced expression of myocardin in iPSC-MSC resulted in their partial transdifferentiation into cardiomyocytes phenotype and improved the electrical conduction during integration with mature cardiomyocytes.published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
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Li, Jing. "Effects of intrinsic & extrinsic factors on the growth and differentiation of human mesenchymal stem cells." View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36434450.
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Jansson, Monika. "Detection of donor cells in recipient tissues after stem cell transplantation using FISH and immunophenotypi Stem cell transplantationng /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-222-4/.
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Hays, Mary Margaret. "Stem cell transplant for sickle cell disease." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12117.
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Thesis (M.A.)--Boston UniversityBackground: Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. As SCD can cause significant morbidity and decrease in life expectancy, further research on curative options is of great interest. Hematopoietic stem cell transplant (HSCT) is the only treatment option offering a chance of cure, but the risks of treatment are not negligible. Because the outcomes of HSCT are best when the procedure is performed at a younger age, understanding what parents know about transplant, their opinion on this option and the risks they are willing to take to achieve a cure is of great value. As sickle cell disease has changed in the United States from a life-threatening condition of childhood to a chronic condition with most of the burden of morbidity and mortality shifted towards adulthood, it is necessary for parents to be fully aware of long term risks and educated on all therapeutic options, so the optimal decision can be made. Objectives: (i) To learn about parents’ recollection and pursuit of further information after undergoing an educational session on risks and benefits of HSCT. (ii) To learn about their worries about transplant and the highest mortality and infertility risks they are willing to accept in order to achieve a cure for their child. (iii) To learn about parents’ readiness to proceed to transplant based on a hypothetical scenario. [TRUNCATED]
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Nadal-Melsio, Elisabet. "Regulatory T cells after allogeneic stem cell transplantation." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523746.
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Li, Victor Chun. "The Cell Cycle and Differentiation in Stem Cells." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10536.
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The relationship between cellular proliferation and differentiation is a major topic in cell biology. What we know comes from models of somatic cell differentiation, where it is widely viewed that cycling and differentiation are coupled, antagonistic phenomena linked at the G1 phase. The extension of this view to stem cells, however, is unclear. One potential possibility is that stem cells also tightly link their G1 phase with their differentiation, indicating a similarity between the differentiation of stem cells and the differentiation of more mature somatic cells. On the other hand, stem cells may utilize different mechanisms or adaptations that confer on them some aspect of uniqueness or "stemness." In this case, stem cells will not exhibit the same coupling with the cell cycle as in many somatic cell models. In this thesis, we examined mouse embryonic stem cells (mESCs), a stem cell that is pluripotent and rapidly cycling with a highly condensed G1 phase. Direct extension of the somatic view posits that elongation of their G1 phase to somatic lengths by cyclin-dependent kinase (CDK) activity inhibition should induce or increase differentiation of these stem cells. Evidence supporting this claim has been contradictory. We show that elongation of the cell cycle and elongation of G1 to somatic lengths is fully compatible with the pluripotent state of mESCs. Multiple methods that lengthen the cell cycle and that target CDK activity or that trigger putative downstream mechanisms (i.e. Rb and E2F activity) all fail to induce differentiation on their own or even to facilitate differentiation. These results indicates that the model of linkage between the G1 phase and differentiation in mESCs is incorrect and leads us to propose that "stemness" may have a physiological basis in the decoupling of cell cycling and differentiation. In summary, we provide evidence that there is a resistance of mESCs to differentiation induced by lengthening G1 and/or the cell cycle. This could allow for separate control of these events and provide new opportunities for investigation and application.
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Mavin, Emily. "Regulatory T cells in haematopoietic stem cell transplantation." Thesis, University of Newcastle upon Tyne, 2014. http://hdl.handle.net/10443/2731.
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Graft-versus-host disease (GvHD) remains the main complication associated with haematopoietic stem cell transplantation (HSCT). GvHD is caused by allo-reactive donor T cells mounting an attack against specific target tissues. CD4+CD25HiFoxp3+ regulatory T cells have been shown to modulate GvHD in vitro and also in vivo animal models. More recently early stage clinical trials have described the successful use of Treg to reduce the incidence of GvHD following HSCT. The aim of this study was to investigate further the suppressive mechanisms by which Treg are able to modulate GvHD and assess the influence of Treg on the beneficial graft-versus-leukaemia (GvL) effect therefore providing further insight into the use of Treg in the therapeutic management of GVHD. Data presented in this thesis demonstrates the successful isolation and expansion of a highly pure Treg population which maintained suppressive capacity throughout culture. We also confirmed that Treg retain suppressive capacity following cryopreservation resulting in reduced workload and increased consistency when used for in vitro functional studies. We also provide the first human in vitro evidence that Treg are able to prevent cutaneous GvH reaction by blocking the migration of effector T cells into the target tissues. The presence of Treg during allo-stimulation caused reduced effector cell activation, proliferation, IFNγ secretion and decreased skin homing receptor expression. Further investigation into the Treg modulation of dendritic cells demonstrated, for the first time in experimental in vitro human GvHD, that this was due to ineffective effector T cell priming in the presence of Treg caused by impairment of dendritic cell functions. Comprehensive phenotypic and functional analysis of Treg treated moDC showed their decreased antigen processing ability and allostimulatory capacity, resulting in a less severe GvH reaction in the skin explant model. Furthermore, this work has revealed that despite Treg impairing in vitro GvL mechanisms at a cellular level there was no association observed between increased Treg levels and the incidence of relapse in a small clinical cohort of HSCT patients. In conclusion this study has provided further insight into the mechanisms by which Treg are able to modulate GvHD. This would inform future clinical trials using Treg as a therapeutic alternative to current GvHD treatment and prophylaxis.
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Harrison, Sean. "Liver cell types derived from pluripotent stem cells." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/liver-cell-types-derived-from-pluripotent-stem-cells(7f39c3ec-facd-4c06-ab9a-7c171313eb05).html.
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Liver development involves the differentiation and interaction of both endoderm and mesoderm cell types. The role of the liver in drug metabolism makes it an important area of medical research. Mimicking embryonic liver development in vitro using human ESCs is a strategy used to differentiate liver cell types. These can then be used as a model playing a role in the development of drugs and the study of their hepatotoxicity and would also have potential for use in cell therapy and regenerative medicine. Differentiated hepatocyte-like cells were found to have more in common with liver cells than those of other organs, including the secretion of albumin and activity of proteins important in drug metabolism, CYP3A and CYP2D6. However the hepatocyte-like cells were found to more closely resemble fetal rather than adult hepatocytesOrganoid differentiation resulted in cells types which in vivo are both endoderm and mesoderm derived cells of the liver. Culture in this 3D system allowed the spontaneous acquisition of polarity by these cells and their formation into structures reminiscent of liver architecture. After treatment with the toxin 4,4′-diaminodiphenylmethane a cell type and structure specific dose response was observed which matches that described in vivo.
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Kemp, Kevin Charles. "The role of mesenchymal stem cells in stem cell transplantation for haematological malignancies." Thesis, University of the West of England, Bristol, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.495521.
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Haemopoietic recovery after high dose chemotherapy (HOC) in the treatment of haematological disease may be slow and/or incomplete. This is generally attributed to progressive haemopoietic stem cell failure, however we hypothesize that HOC induced defective haemopoiesis may be in part due to poor stromal function. Although chemotherapy is known to damage mature bone marrow stromal cells in-vitro, the extent to which marrow mesenchymal stem cells (MSC) are damaged by HOC in-vivo and in-vitro is unknown. To firstly address this question the physical characteristics and functional properties of marrow MSC derived from patients who have received chemotherapeutic treatment for various haematological diseases were investigated. Subsequently a suitable in-vitro treatment culture model was developed and the effects of chemotherapy exposure in-vitro using cell culture and proteomic techniques were shown. Results of this study demonstrate proliferative and phenotypic changes to patient MSC caused by HOC regimens. In contrast, the differentiation capacity, and ability to form functional marrow stroma after exposure to HOC in-vivo was equal to that of patient MSC studied prior to HOC. Chemotherapeutic exposure to MSC cultures in-vitro have confirmed changes seen in-vivo, with abnormalities evident in MSC proliferation, differentiation and also in their ability to support haemopoietic stem cell migration and repopulation after treatment. A reduced C044 expression on MSC, after exposure to cyclophosphamide, was also observed and the importance of this molecule shown through con-focal microscopy demonstrating its interaction with C034+ haemopoietic stem cells. Using proteomic techniques differences in protein expression by MSC, relating to changes in their function after chemotherapy exposure, were also observed after treatment with cyclophosphamide or melphalan. Finally the role of keratinocyte growth factor as a potential cyto-protective agent to MSC against damage caused by chemotherapy exposure was tested. Results indicated there was significant evidence to indicate that KGF was able to preserve reductions in C044 expression levels after MSC exposure. It was concluded that marrow MSC sustain prolonged injury due to recurrent courses of HOC in-vivo and in-vitro. However, the clinical importance of the chemotherapy induced defects we have observed must be determined through the initiation of prospective randomized trials of the effects of MSC co-transplantation on haemopoietic recovery in the setting of HOC with and without haemopoietic stem cell rescue.
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Lin, Wenyu. "Investigating the immunomodulatory properties of human embryonic stem cell-derived mesenchymal stem cells." Thesis, Imperial College London, 2010. http://hdl.handle.net/10044/1/7060.
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The immunosuppressive property of mesenchymal stem cells (MSC) has been utilised to ameliorate autoimmune reactions such as graft-versus-host disease. However, variation exists in primary MSC isolated due to differences in donor age and tissue of origin. Alternatively, human embryonic stem cells (hESC) can be differentiated to homogeneous populations of MSC (hESCMSC), thus providing an unlimited source of MSC for cell therapy. In this study, the immunomodulatory properties of two hESC-MSC lines, hESC-MSC1 and hESC-MSC2, were compared with adult bone marrow-derived MSC (BM-MSC) and neonatal foreskin fibroblast (Fb). hESC-MSC were able to suppress the proliferation of anti-CD3/CD28-stimulated CD4+ T cells in contact and transwell systems. The immunosuppression was demonstrated by both the carboxyfluorescein diacetate succinimidyl ester (CFSE) and [3H]- thymidine proliferation assays. However, hESC-MSC were less potent and twice the number of adherent hESC-MSC (as measured by IC50) compared to BM-MSC and Fb were required to suppress T cell proliferation by 50%. Supernatants collected from transwells of MSC or Fb with T cells were shown to suppress T cell proliferation, suggesting that suppressive factors were only produced in the presence of activated T cells. Among several candidates, endothelial monocyte-activating polypeptide-II (EMAP-II) was identified as a potential suppressive factor. T cells also induced indoleamine-2,3- dioxygenase (IDO) expression in MSC and Fb. IDO led to the depletion of tryptophan, an essential amino acid, and/or the production of tryptophan metabolites (kynurenines), thereby inhibiting T cell proliferation. Interestingly, blocking of IDO with 1-methyltrytophan reversed the suppressive effect, implicating IDO as a potential mediator in T cell suppression. Concomitantly, several candidate suppressive factors in the supernatants have also been identified using antibody arrays. However, their functions require validation. In conclusion, hESC-MSC share similar suppressive properties as BM-MSC and represent a potential cell source for clinical purposes.
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Vicario, Nunzio. "Directly induced Neural Stem Cells transplantation and prospects for stem cell-based therapy." Doctoral thesis, Università di Catania, 2017. http://hdl.handle.net/10761/4088.
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Despite the remarkable beneficial effects of disease-modifying agents in relapsing-remitting multiple
sclerosis (MS) patients, progressive forms of (P)MS still lack effective treatments. This stark contrast is
partially dependent on the difficulties researchers have found in tackling the complex pathophysiology of this
phase of disease, in which chronic inflammation within the central nervous system (CNS) is coupled by
ongoing neurodegeneration and demyelination.
Cell transplantation is among the most promising therapeutic approaches in regenerative medicine,
combining tissue trophic and immunomodulatory effects of the graft with its intrinsic potential for cellreplacement.
These are all attributes that can be harnessed to treated patients with PMS.
As such, within this thesis, I have focused my attention on investigating how cellular therapies could be used
to (i) prevent neuronal damage, (ii) modulate the chronic activation of the immune system and (iii) replace
the damaged myelin in PMS.
Olfactory Ensheathing Cells (OECs) are a special population of glial cells known to exert neuroprotective
mechanisms and capable of promoting neuroprotection. Using in vitro models of neuron-like cells, I have
demonstrated that OECs exert their neuroprotective effect by reducing Cx43-mediated cell-to-cell and cell-toextracellular
environment communications. Despite this important finding, the immunomodulatory and
remyelinating potential of OECs is still limited. As such, I decided to study a complementary stem cell
approach that conjugates these attributes with ease in clinical applicability.
Induced Neural Stem Cells (iNSCs) are a source of autologous, stably expandable, tissue specific and easily
accessible stem cells, which have the potential to differentiate into the three main neural lineages. Mouse
iNSCs were characterized in vitro and in vivo and their immunomodulatory potential was initially studied. This
work uncovered a novel mechanism that underpins the potential of iNSCs to interact with the chronic CNS
compartmentalised activation of the innate immune system. Specifically, I found that iNSCs are able to
sense extracellular metabolites, which accumulate in the chronically inflamed CNS, and to ameliorate
neuroinflammation via succinate-SUCNR1-dependend mechanisms. To characterize the potential for tissue
replacement and remyelination of such a promising cell line, I have also analysed how iNSCs grafts
differentiate in an experimental model of focal demyelination. I found that iNSCs are able to integrate and
differentiate into remyelinating oligodendrocytes (OLs) in chronic demyelinated CNS. These data suggest
that iNSCs are indeed an effective source of stem cell transplantation, being able to modulate inflammation
and to effectively replace lost tissue in mouse models of PMS.
Altogether the evidences gathered in this thesis are important new steps in the field of cell transplantation,
which will be pivotal in the march forward for future clinical applications in chronic demyelinating CNS
disorders.
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Mittal, Nikhil 1979. "Cell-cell and cell-medium interactions in the growth of mouse embryonic stem cells." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/62602.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2010.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (p. 100-108).
Embryonic stem cells serve as powerful models for the study of development and disease and hold enormous potential for future therapeutics. Due to the potential for embryonic stem cells (ESCs) to provide a variety of tissues for use in regenerative medicine, there has been great interest in the identification of factors that govern the differentiation of ESCs into specific lineages. Much of this research builds on previous studies of the role of intercellular signaling in the specification of various cell types in the developing embryo. However, relatively little work has been done on understanding the role of cell-cell communication in the self-renewal of ESCs. In the first part of this thesis I describe the development and testing of new devices for studying intercellular signaling - the nDEP microwell array and the Bio Flip Chip (BFC). We used the BFC to show that cell-cell interaction improves the colony-forming efficiency and the self-renewal of mouse ESCs. Further, we demonstrate that the interaction is at least partly diffusible. In the next part of the thesis I describe our use of more traditional assays to validate the results obtained using the BFC and to further explore the role of diffusible signaling in the survival of mouse ESCs. We demonstrate the existence of an optimal density for 2-day culture of mouse ESCs. Further, we demonstrate that the increase in growth with plating density (103-104 cells/cm2) is at least partly due to the existence of one or more survival-enhancing autocrine factor(s) in mouse ESC cultures, and that one of these factors is Cyclophilin A. Finally, we demonstrate that changes in the low molecular weight composition of the medium are likely responsible for the decrease in growth at high plating densities (>104 cells/cm2). We use a numerical model to show that competition between the positive effect (on growth) of autocrine survival factors and the negative effect of nutrient depletion can account for the observed optimal growth density. Our study provides new insight into the processes underlying, and optimization of, growth in cell types that lack contact inhibition such as cancer cells and stem cells.
by Nikhil V. Mittal.
Ph.D.
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Ishikura, Yukiko. "In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225510.
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Zannettino, Andrew Christopher William. "Molecular definition of stromal cell-stem cell interactions /." Title page, contents and summary only, 1996. http://web4.library.adelaide.edu.au/theses/09PH/09phz32.pdf.
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Meletis, Konstantinos. "Studies on adult stem cells /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-803-7/.
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Götherström, Cecilia. "Characterisation of human fetal mesenchymal stem cells /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-139-3/.
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Saleh, Lubaid. "Small molecule mediated targeting of haematopoietic stem/progenitor cell and leukaemic stem cell function." Thesis, Cardiff University, 2017. http://orca.cf.ac.uk/105172/.
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Haematopoietic stem cells (HSC) are a rare population of cells that have the ability to self-renew and differentiate giving rise to various blood lineages, thereby reconstituting the whole haematopoietic system. This is an essential characteristic, exploited in bone marrow transplantation therapy in response to myeloablative treatment. Due to their rarity, the lack of sufficient HSC numbers for transplantation has proved to be a major clinical issue. Separately, in the development of leukaemia, acquired mutations in HSCs give rise to malignant cells. These cells, like HSCs, have the ability to self-renew and differentiate forming immature blasts and are termed cancer (leukaemic) stem cells. They are thought to remain in a quiescent state and are therefore not targeted by standard chemotherapy, inducing relapse in haematopoietic malignancies. In this study, a cross species stem cell based screen was conducted on a 12,000 small molecule library across a range of adult and embryonic tissue types with a view to identifying compounds that would (i) expand HSCs ex vivo and in vivo for transplantation and (ii) eradicate cancer stem cells in leukaemia. A number of small molecules were identified as lead compounds and were assessed in our investigation. We found that Yohimbine, an alpha-2 adrenergic receptor (adra-2) antagonist, and Oxa-22, cis-2-Methyl-5-trimethylammoniummethyl-1,3-oxathiolane iodide (M3 Muscarinic acetylcholine receptor agonist) elicited a 2- and 1.5- fold increase in HSC frequency (respectively) in vivo. Further competitive transplantation studies showed that Yohimbine and Oxa-22 treated cells also enhanced the reconstitution of B cells and T cells respectively. In parallel, we also assessed Oxa-22 and a third compound, Phthalylsulfathiazole- an antibacterial sulphonamide, in the leukaemic setting to ascertain whether compounds could target leukaemic stem cells (LSCs). We found that these compounds promoted proliferation in acute myeloid leukaemia (AML) cell lines. Furthermore, when Oxa-22 and Phthalylsulfathiazole were administered in vivo models of AML, they accelerated disease progression by increasing the number of LSCs. Collectively, these results show that using small molecules we can target neuronal related pathways to enhance HSC number and function. Further investigation is required to elucidate the exact mechanisms of the compounds however, these data may prove to be influential in directing new methods of stem cell expansion for transplantation therapies. Small molecules targeting neuronal or antibacterial related pathways were also found to target malignant LSCs and alter their behaviour. By driving LSCs out of their dormant state, these small molecules may pave the way for potential targeting of LSCs in conjuction with standard current chemotherapies that incorporate and kill proliferating cancer cells.
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Elseed, Mohammed. "Investigation of periodontal stem cell attachment to dentin and dental pulp stem cell migration." Thesis, NSUWorks, 2007. https://nsuworks.nova.edu/hpd_cdm_stuetd/12.
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McGarvey, Alison Clare. "Genome-wide transcriptional characterisation and investigation of the murine niche for developing haematopoietic stem cells." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28741.
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Haematopoietic stem cells (HSCs) are capable of differentiation into all mature haematopoietic lineages, as well as long-term self-renewal and are consequently able to sustain the adult haematopoietic system throughout life. Currently, in the mouse, HSCs are understood to first appear in the aorta-gonad-mesonephros (AGM) region at embryonic day 11 via a process of maturation from precursors (pre-HSCs). This maturation within the AGM region involves the complex interplay of signalling between cells of the niche and maturing precursor cell populations, but is relatively little understood at a molecular level. Recently our understanding of the AGM region has been refined, identifying the progression from E9.5 to E10.5 and the polarity along the dorso-ventral axis as clear demarcations of the supportive environment for HSC maturation. In this thesis, I investigated the molecular characteristics of these spatio-temporal transitions in the AGM region through the application of RNA-sequencing. This enabled the identification of molecular signatures which may underlie the supportive functionality of the niche. I further compared these expression signatures to the transcriptional profile of an independent cell type, also capable of supporting HSC maturation, the OP9 stromal cell line. By combining this transcriptional information with an ex vivo culture system, I screened a number of molecules for their ability to support HSC maturation from early precursors, leading to the discovery of a novel regulator of HSC maturation: BMPER. Further characterisation of this molecule enabled the identification of its specific cellular source and the proposal that through its action as an inhibitor of BMP signalling it facilitates the maturation of precursors into HSCs. These results lend further detail and support to the role of BMP signalling in the regulation of HSC maturation as well as demonstrating the potential of these transcriptional profiles to yield novel mechanistic insight.
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Kim, Narae. "External pH in culture on somatic cell reprogramming and cell differentiation in mouse and chicken cells." Kyoto University, 2017. http://hdl.handle.net/2433/218018.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第20092号
農博第2199号
新制||農||1046(附属図書館)
学位論文||H29||N5026(農学部図書室)
33208
京都大学大学院農学研究科応用生物科学専攻
(主査)教授 今井 裕, 教授 松井 徹, 教授 久米 新一
学位規則第4条第1項該当
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Ismail, Siti N. "Stem cell bioprocessing : the bioengineering of lung epithelium in 3D from embryonic stem cells." Thesis, Imperial College London, 2009. http://hdl.handle.net/10044/1/9013.
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Stem cell therapies and tissue engineering strategies are required for the clinical treatment of respiratory diseases. Previous studies have established protocols for the differentiation of airway epithelium from stem cells but have involved costly and laborious culture methods. The aim of this thesis was to achieve efficient and reproducible maintenance and differentiation of embryonic stem cells to airway epithelium, in 2D and 3D culture, by developing appropriate bioprocessing technology. Firstly, the 2D differentiation process of human and murine ES cells into pulmonary epithelial cells was addressed. The main finding in was that the proportion of type II pneumocytes, the major epithelial component of the gas-exchange area of lung, differentiated with this method was higher than that obtained in previous sudies, 33% of resultant cell expressed the specific marker surfactant protein C (SPC) compared with up to 10%. Secondly, the maintenance and differentiation was carried out in 3D. A protocol was devised that maintained undifferentiated human ES cells in culture for more than 200 days encapsulated in alginate without any feeder layer or growth factors. For ES cell differentiation in 3D, a method was devised to provide a relatively cheap and simple means of culture and use medium conditioned by a human pneumocyte tumour cell line (A549). The differentiation of human and murine ES cells into pulmonary epithelial cells, particularly type II pneumocytes, was found to be upregulated by culture in this conditioned medium, with or without embryoid body formation. The third step was to test whether this differentiation protocol was amenable to scale-up and automation in a bioreactor using cell encapsulation. It was possible to show that encapsulated murine ES cells cultured in static, co-culture or rotating wall bioreactor (HARV) systems, differentiate into endoderm and, predominantly, type I and II pneumocytes. Flow cytometry revealed that the mean yield of differentiated type II pneumocytes was around 50% at day 10 of cultivation. The final stage of the work was to design and produce a perfusion system airlift bioreactor to mimic the pulmonary microenvironment in order to achieve large scale production of biologically functional tissue. The results of these studies thus provide new protocols for the maintenance of ES cells and their differentiation towards pulmonary phenotypes that are relatively simple and cheap and can be applied in bioreactor systems that provide for the kind of scale up of differentiated cell production needed for future clinical applications.
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Fijnvandraat, Arnoldus Cornelis. "Embryonic stem cell-derived cardiomyocytes." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2003. http://dare.uva.nl/document/68354.
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Skinner, Elizabeth Mary. "Pluripotent stem cell-derived endothelial cells for vascular regeneration." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/15865.
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Background: Vascular endothelial dysfunction plays a major role in the pathogenesis of atherosclerosis. As such, the study of endothelial cells has sought to identify causal pathways and novel therapeutic approaches to promote vascular repair. Induced pluripotent stem (iPS) cell technology may be a particularly useful tool, and could be used to derive endothelial cells and their progenitors from individuals with endothelial dysfunction to explore these pathways and develop novel strategies for vascular regeneration. Whilst iPS cells are conventionally obtained from the reprogramming of dermal fibroblasts, it was hypothesised that endothelial cells could also be reprogrammed, and that these pluripotent cells would have enhanced capacity for endothelial differentiation and vascular regeneration. Objectives: To generate iPS cells from human fibroblasts and endothelial cells and to assess their potential for endothelial differentiation and vascular regeneration. Methods and Results: A) Reprogramming: Dermal fibroblasts and endothelial outgrowth cells from blood were obtained from healthy donors (n=5) and transfected with episomal vectors containing six reprogramming factors: Sox2, Klf4, Oct3/4, L-Myc, Lin28 and Shp53. Successfully reprogrammed fibroblast-derived iPS (fiPS) and endothelial cell-derived iPS (eiPS) arose as colonies, and were isolated and expanded. Reprogrammed cells expressed pluripotency markers SSEA3, SSEA4, TRA 1 60, Oct3/4 and NANOG, and developed into all three germ layers following embryoid body formation. B) Endothelial differentiation: iPS and ES cell lines were aggregated into embryoid bodies in stem cell growth media containing mesoderminducing cytokines. Embryoid bodies were then disaggregated and cultured in endothelial medium supplemented with VEGF. After seven days, a population of CD31+ cells was isolated and further cultured. Mature endothelial cell antigen expression was confirmed by flow cytometry. CD31+ cells were similar to mature endothelial cells in functional assays of proliferation, migration, nitric oxide production and angiogenesis. C) Comparison of fiPS versus eiPS: eiPS differentiated into endothelial cells with greater efficiency than fiPS (21±3% versus 3±2%, P < 0.05). fiPS-derived endothelial cells and eiPS-derived endothelial cells expressed similar levels of endothelial markers CD146, CD31, VEFGR2 and CD34 compared to control endothelial cells. When grown on Matrigel, they formed tubule-like structures with a similar number of vessel connections. In vivo, endothelial cells derived from fiPS and eiPS increased neovasculogenesis in a nude mouse model: vessel density was increased after implantation of endothelial cells from fiPS and eiPS by 3.50 vessel counts (P≤0.001) and 3.47 vessel counts (P≤0.001) respectively, when compared to controls. By comparison control endothelial cells did not increase vessel density compared to control (P > 0.05). Conclusions: Endothelial cells can be isolated from blood and reprogrammed to form pluripotent stem cells with enhanced capacity to differentiate into endothelial cells than those derived from dermal fibroblasts. Endothelial cells derived from both sources promote angiogenesis in vivo, and have major potential for therapeutic applications in vascular regeneration.
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Prater, Michael David. "Progenitor and stem cell potential of mammary myoepithelial cells." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648364.
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Giraddi, Rajashekharagouda. "Cell cycle kinetics of mammary stem and progenitor cells." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607789.
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Pannérec, Alice. "The skeletal muscle stem cell niche : defining hierarchies based upon the stem cell marker PW1 to identify therapeutic target cells." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00833422.
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Les cellules satellites permettent la réparation des muscles squelettiques, mais chez les patients atteints de myopathies ces cellules ne fonctionnent pas correctement ce qui conduit à l'atrophie musculaire. Nos travaux ont montré qu'une nouvelle population de cellules souches musculaires, les PICs, favorisent la prolifération des cellules satellites par l'intermédiaire de la follistatine qui contrebalance l'effet négatif de la myostatine. Lorsque la myostatine est inactivée chez des souris par injection d'inhibiteur, le nombre de PICs augmente considérablement et les animaux présentent des muscles hypertrophiés. De récentes études ont montré que la régénération musculaire est impossible sans les cellules satellites, mais si nous inactivons la myostatine dans ces animaux la régénération musculaire est restaurée. Nous postulons que les PICs ont permis cette réparation et constituent donc une bonne cible pour des molécules pharmacologiques à visée thérapeutique
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Maggs, Luke. "The role of stem cell graft derived natural killer cells in regulating patient outcomes from allogeneic haematopoietic stem cell transplantation." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8633/.
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Myeloid and lymphoid malignancies are potentially curable through a graft versus leukaemia (GvL) effect following allogeneic haematopoietic stem cell transplantation. Whilst donor T cell are thought to be the main mediators of GvL, the effect of donor NK cells within HLA matched T cell depleted transplant setting is more unclear. Patient blood samples were analysed during the first month post-transplant, with higher reconstitution of NK cells at two weeks conferring a relapse protection association. Donor stem cell graft samples, from which NK cells within the patient at two weeks are thought to be derived, similarly displayed a strong association between high NK cell dose and protection from disease relapse. CD56dimDNAM+ NK cells were found to be the population with the most significant association. The ability of NK cells to kill AML blasts in a DNAM dependent manner was shown indicating that direct killing of residual tumour cells may be a valid mechanism of GvL. These findings suggest that optimising the number of NK cells within stem cell grafts should be considered as a means to prevent disease relapse.
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Pannerec, Alice. "The skeletal muscle stem cell niche : defining hierarchies based upon the stem cell marker PW1 to identify therapeutic target cells." Paris 6, 2012. http://www.theses.fr/2012PA066440.
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Les cellules satellites permettent la réparation des muscles squelettiques, mais chez les patients atteints de myopathies ces cellules ne fonctionnent pas correctement ce qui conduit à l’atrophie musculaire. Nos travaux ont montré qu’une nouvelle population de cellules souches musculaires, les PICs, favorisent la prolifération des cellules satellites par l’intermédiaire de la follistatine qui contrebalance l’effet négatif de la myostatine. Lorsque la myostatine est inactivée chez des souris par injection d’inhibiteur, le nombre de PICs augmente considérablement et les animaux présentent des muscles hypertrophiés. De récentes études ont montré que la régénération musculaire est impossible sans les cellules satellites, mais si nous inactivons la myostatine dans ces animaux la régénération musculaire est restaurée. Nous postulons que les PICs ont permis cette réparation et constituent donc une bonne cible pour des molécules pharmacologiques à visée thérapeutiqueSatellite cells are considered the major source of muscle progenitors, however, other populations with myogenic popential have been discovered. We have identified a new muscle-resident non-satellite cell population, termed PICs, which can differentiate into three different lineages, skeletal muscle, smooth muscle and fat. PICs rescue satellite cells from myostatin inhibition in vitro through follistatin release. When myostatin is inactivated in vivo, PICs number is markedly increased and mice display hypertrophied muscles. While recent studies have demonstrated that muscle regeneration cannot occur without satellite cells, we show that muscle regeneration is restored when mice have been previously treated with a myostatin inhibitor. We postulate that PICs have participated in muscle repair rescue, and thus constitute an interesting population to be targeted for pharmaceutical strategies aimed at improving skeletal muscle mass and function
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Lu, Xibin, and 盧希彬. "Quantitative characterization of mouse embryonic stem cell state transition." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208049.
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Batsivari, Antoniana. "Studying the cell cycle status during haematopoietic stem cell development." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25802.
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In adults blood stem cells, called haematopoietic stem cells (HSC), give rise to all blood cells throughout life. The origin and biology of HSCs during embryo development has been an intensely studied topic. Definitive HSCs are generated intra-embryonically in the aorta-gonad-mesonephros (AGM) region of the mid-gestation embryo. Recent research revealed that HSCs emerge through multistep maturation of precursors: proHSC → preHSC I → preHSC II → definitive HSC (dHSC). A hallmark of the HSC emergence is the appearance of intra-aortic haematopoietic clusters that are considered to be sites of haematopoiesis. It was shown in vitro that the E11.5 HSCs are slowly cycling compared to progenitor cells. However, cell cycle status and its role during early HSC development remain unclear. Here I used Fucci transgenic mice that enable in vivo visualisation of the cell cycle. Functional and phenotypic analysis showed that in the early embryo the proHSC precursors cycle slowly, whereas committed progenitors are actively cycling. Meanwhile the preHSC I precursors arising in the E10.5 AGM region become more rapidly cycling. They are located closer to the luminal cavity of the dorsal aorta, while their ancestors, the proHSCs, are slowly cycling and are located at base of the clusters. Furthermore, in the mid-gestation embryo the preHSC I become slowly cycling and are closer to the endothelial lining of the aorta, while they give rise to the actively cycling preHSC II that are located to the luminal area of the artery. Finally, definitive HSCs are mainly slowly cycling at this stage like their foetal liver counterparts. As expected, HSCs in adult bone marrow are mainly dormant. The data suggest that transition from one precursor type to another is accompanied by distinct changes in cell cycle profile and that HSCs become progressively quiescent during development. To test the role of cell cycle in HSC maturation, we used inhibitors against signalling pathways known to play important roles in HSC development. Notch inhibitor affected the cell cycle status of haematopoietic precursors, by possibly promoting them to rapidly proliferate and potentially blocking the maturation from preHSC I to preHSC II precursors. Shh antagonist had the opposite effect and enhanced the HSC activity from the preHSC I precursors. Altogether these results suggest that the cell cycle status plays an important role in the HSC development. A better understanding of the molecules that control this process will allow us to optimize the culture condition for generation of functional HSCs in the laboratory.
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Fok, Elsie. "Advanced stem cell delivery systems for the treatment of corneal epithelial limbal stem cell deficiency." Thesis, University of Brighton, 2014. https://research.brighton.ac.uk/en/studentTheses/134e3b10-9910-40d6-bec8-8a7481b9e67e.
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Limbal stem cell deficiency (LSCD) can be treated successfully using ex vivo limbal epithelial stem cells (LESC) derived from cadaveric donor tissue. However, shortages in such tissues and graft rejection, resulting from inflammation, are persistent issues. The purpose of this study was to optimize current culturing techniques used for LESC transplant tissue, considering expansion and cryopreservation issues surrounding the establishment of a stem cell bank. In addition, a novel anti-inflammatory biomimetic peptide was investigated to address issues surrounding amnion and steroid use in LESC transplantation, inflammation and transplant rejection. Cell cultures derived from Optisol and organ culture stored tissues were examined for optimum growth, characterized by an ability to grow to 70 % to 80 % confluence while maintaining epithelial cell morphology and the presence of positive and negative LESC markers (K3, K19, p63 and PAX-6) as identified by immunocytochemical staining and QRT-PCR. Furthermore, the effect of culture expansion and cryopreservation on stem cell characteristics was examined. A short chain IL-l receptor antagonist peptide was synthesized and characterized using mass spectroscopy (MS), high performance liquid chromatography (HPLC) and liquid chromatography-mass spectroscopy (LC-MS). Anti-inflammatory properties were investigated using ELISA detection of IL-8, IL-6 and IL- l ~ in keratocytes and LESC following stimulation with either lipopolysaccharide or recombinant human IL- l~. Feasible delivery of cells and peptide on a contact lens was investigated to assess the possibility of an "all in one" graft. Results showed that organ culture stored tissues can provide 100 % successful cell cultures using current techniques in terms of reaching confluence and maintaining LESC morphology and phenotype. Sub-culturing and cryopreservation of cultures however did not produce confluent cell sheets, as required for clinical application. The anti-inflammatory peptide was shown to effectively suppress production of key inflammatory cytokines in LESC and keratocytes by acting as an IL- l receptor antagonist and interrupting the IL- l inflammatory pathway. Binding of the peptide to the contact lens was shown to be possible. Such a scaffold also supported expansion of LESC. However, the 2.7 nmol of peptide bound to the lens did not significantly lower cytokine production. Findings suggest that it is possible to culture adequate numbers of LESC for the initiation of a stem cell bank using current techniques. However, modifications to culturing methods are needed to ensure successful sub-culturing and cryopreservation. The peptide has been shown to be effective in reducing inflammatory cytokine production, providing a possible alternative to steroids. An a11-in-one graft could provide a key development in treating LSCD. However further work is required to optimize the peptide concentration to allow effective inflammation control.
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Hsiao, Lien-Cheng. "Cardiac stem cell therapy for heart failure." Thesis, University of Oxford, 2012. https://ora.ox.ac.uk/objects/uuid:c4fcb449-2d05-4dc6-9a8d-f7450c0b200c.
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Cardiovascular disease is a leading cause of death worldwide and becomes increasingly prevalent in the elderly population. Independent of etiopathogenesis, heart failure (HF) is the final common stage of numerous heart diseases. Cardiac stem cell (CSC) therapy has emerged as a promising cell-based strategy for treatment of HF. However, cell replacement is not able to fully restore a structurally damaged myocardium in advanced and end-stage HF. The objective of this project was to test the following hypotheses: that a bioengineered heart extracellular matrix (ECM) with preserved intact geometric structure could be generated using decellularization by coronary perfusion; and that autologous CSCs, to repopulate this ECM, could be isolated and expanded from the adult heart, with the caveat that autologous CSCs are depleted and impaired by both aging and chronic dilated cardiomyopathy. This will help to develop a possible therapeutic approach for advanced HF, using a combination of CSCs and engineering technique. Resident CSCs were isolated from explant-derived cells (EDCs) and expanded into cardiosphere-derived cells (CDCs) via cardiosphere formation. The CDCs expressed CSC markers (c-kit and Sca-1), pluripotent markers (Oct3/4 and Sox2), and the cardiac lineage-committed marker (Nkx2.5), and showed clonal expansion, self-renewal, and cardiomyogenic potential in vitro. In tissue engineering experiments, CDCs survived and proliferated within biomaterial alginate scaffolds for up to 7 weeks. An engineered bioartificial ECM scaffold was successfully produced from a whole rat heart using retrograde coronary perfusion and possessed an intact 3D architecture with functionally perfusable vascular network. Compared with ventricles, cultures derived from atria produced significantly higher number of c-kit+ and Sca-1+ CSCs (c-kit: 13% vs. 3.4%; Sca-1: 82% vs. 53%, respectively) and exhibited greater clonogenic and proliferative capacity. CDCs could be grown from young and aged mice, but the yield of CSCs significantly declined with age, as did cell migration and differentiation potential. In comparison to wild-type mice, atrial-CDCs from dystrophic mice showed no significant differences in CSC subpopulations and characteristics, despite confirmation of cardiac dysfunction using MRI. In conclusion, CDCs could be considered to be a viable cell candidate for cardiac therapy and may be used to treat HF at various stages, in combination with myocardial tissue engineering.
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Reimer, Andreas Sven. "Analysis of stem cell interactions at single cell resolution." Thesis, King's College London (University of London), 2015. https://kclpure.kcl.ac.uk/portal/en/theses/analysis-of-stem-cell-interactions-at-single-cell-resolution(feddcc15-74b4-4d32-874e-93a25ec92f0d).html.
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As a stem cell divides, two daughter cells are produced that either possess stem cell characteristics or become a cell with a more specialized function. Cellular markers have been identified that can be used to describe the phenotype of stem cell progeny. However, the development of tools that allow the description of cellular phenotypes remains a challenge due to the complexity of cellular heterogeneity. In my thesis, I address this problem by developing a phenotyping platform that stimulates cells to either remain in a stem cell state or become a cell with a more specialized func-tion. Multi-well plates were used to create microenvironments that resemble the natural surroundings of stem cells in tissues. High-resolution imaging technology was used to capture the cellular state after exposure to these microenvironments. High-content analysis was applied to generate a detailed description of every cell in the assay. Subsequently, mathematical modelling was used to describe the cell phenotyping profile in each environment. These profiles were then compared to characterise the cellular response to each environment. High-throughput technology was used to understand how topography features affect proliferation of pluripotent stem cells in a xeno-free environment. An algorithm was used to predict whether any given topography will support the pluripotent state. A second algorithm was used to predict an optimised topography. In the final part of my thesis, primary mouse skin fibroblasts and neural progenitor cells that were derived from human iPS cells were exposed to extrinsic cues in cellular assays. While distinct fibroblast subpopulations from neonatal mouse back skin responded to the assay irrespective of media conditions, human iPS cell-derived neural progenitor cells required the ad-dition of extrinsic cues to induce a self-renewal response. Therefore, it is possible to produce neural progenitor cells in vitro and study stem cell characteristics that are known to occur in an in vivo context.
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Erlandsson, Anna. "Neural Stem Cell Differentiation and Migration." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl.[distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3546.
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Lynch, Thomas John. "Adult stem cells in the trachea and tracheal submucosal glands." Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/6464.
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Breathing is essential for human life, yet tens of millions of people in the U.S. alone suffer from lung diseases. With each breath, lungs are exposed to the external environment. Inhaled air first passes through the trachea, bronchi, and finally the bronchioles before it reaches the alveoli where gases are exchanged. A barrier of epithelial cells protects the airways. In addition, epithelial glands also secrete protein-rich fluids onto the airway surfaces to help maintain sterility. Injury, disease, or other factors can damage these cells, and regiospecific stem cells (SCs) can divide to replace them. However, many important details about lung SCs are still unknown. For example, what processes control SC division? How do region-specific SCs differ from one another? And how does disease or injury impact SC biology? We found that some processes that regulate lung development also control adult SC division following injury. We show that SCs from airway glands give rise to surface epithelial cell types and glandular cell types. In contrast, surface SCs only generated surface cell types. Finally, we identify a type of cell in the glands that can regenerate surface cell types after severe injury. These studies provide new insights into the neighborhoods in which SCs reside in the large airways and processes that control their contribution to airway repair following injury. Overall, this research provides important new insights into adult SC biology and conditions affecting lung health.
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Carlén, Marie. "Adult neurogenesis : from stem cell to functional neuron /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-367-1/.
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Carr, Jonathon M. "Heterogeneity within the stem cell compartment : impact on fate determination of human pluripotent stem cells." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/20386/.
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Che, Mohamad Che Anuar. "Human embryonic stem cell-derived mesenchymal stem cells as a therapy for spinal cord injury." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/7047/.
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Traumatic injury to the spinal cord interrupts ascending and descending pathways leading to severe functional deficits of sensory motor and autonomic function which depend on the level and severity of the injury. There are currently no effective therapies for treating such injuries and the adult central nervous system has very limited capacity for repair so that recovery is very limited and functional deficits are usually permanent. Cell transplantation is a potential therapy for spinal cord injury and a range of cell types are being investigated as candidates. Mesenchymal stem cells (MSCs) obtained from bone marrow are one cell type quite extensively studied. When transplanted into animal models of spinal cord injury these cells are reported to affect various aspects of repair and in some cases to improve functional outcome according to behavioural measures. However, the use of these cells has several limitations including the need for an invasive harvesting procedure, variability in cell quality and slow expansion in culture. This project therefore had two main aims: Firstly to investigate whether MSC-like cells closely equivalent to bone marrow derived MSCs could be reliably and consistently differentiated from human embryonic stem cells (hESCs) in order to provide an “off the shelf” cellular therapy product for spinal cord injury and secondly, to transplant such cells into animal models of spinal cord injury in order to, determine whether hESC-derived MSCs replicate or improve on the repair mechanisms reported for bone marrow MSCs.
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Bigdeli, Narmin. "Derivation, characterization and differentiation of feeder-free human embryonic stem cells /." Göteborg : Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, 2010. http://hdl.handle.net/2077/22353.
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Pepperell, Emma E. "The regulation of stem cell engraftment." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:873a14b9-6c7b-4643-bb34-4e1679d4f734.
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The engraftment of haemopoietic stem/progenitor cells (HSPCs) from umbilical cord blood (UCB) into adult recipients, although advantageous in terms of sourcing units, the decreased need to match donor and recipient and reduced risk of graft versus host disease (GvHD), is delayed compared to grafts using HSPCs from mobilised peripheral blood (MPB) or bone marrow (BM). One reason for this is the limited number of HSPCs (CD34+/CD133+ cells) in a unit of UCB compared to MPB or BM. The CXCR4-CXCL12 axis is widely recognised as a key player in the bone marrow homing, retention, and engraftment of HSPCs. The aim of this thesis was to investigate whether the engraftment of HSPCs from UCB into the bone marrow could be improved. Firstly, a novel in vitro 3D time-lapse chemotaxis assay to assess the homing capacity of human UCB CD133+ HSPCs, towards the chemokine CXCL12 was developed. One advantage of this assay was that it distinguished cell chemotaxis from chemokinesis and allowed these parameters to be quantified. Human UCB CD133+ HSPC chemotaxis towards CXCL12 was inhibited by the CXCR4 antagonist, AMD3100. Importantly, the presence of CXCL12 or AMD3100 had no affect on cell chemokinesis. To complement the in vitro chemotaxis assay, a short term in vivo homing assay in NSG mice was successfully established. The effect of siRNA silencing of the CXCR4 co-receptor, CD164, which is also expressed on CD133+ HSPCs, on cell migratory and homing ability was investigated. CD164 knock-down using siRNA in human UCB CD133+ HSPCs did not demonstrate an effect on homing to NSG bone marrow in vivo or chemotaxis to CXCL12 in vitro. However, homing to NSG mouse spleen was significantly reduced in cells silenced for CD164. Following this, an 8 day HSPC expansion system using nanofibre scaffolds (Nanex) and differing cytokines was investigated. These serum and feeder free conditions yielded a significant expansion of cells that retained CD133+CD34+ expression and their in vitro chemotactic ability to CXCL12. Time constraints did not permit the engrafting ability of these cells to be analysed in an in vivo HSC reconstitution assay that was initiated. However these studies will provide the basis to support future related research in this laboratory.
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Malandraki-Miller, Sophia. "Enhancing progenitor cells for cell therapy after myocardial infarction." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:205043f4-e3e0-4947-9afc-b43f1543e0bd.
Full textAbstract:
Based on data from the World Healthcare Organisation, cardiovascular diseases are the primary cause of disease-related death globally, with myocardial infarction (MI) being the most prevalent. If not treated effectively, MI can progress to heart failure (HF). With 70 million prescriptions for HF in 2014 and 515 people in the UK being hospitalised daily with MI, the British Heart Foundation calls for novel robust treatments. Even though cardiac stem cell (CSC) therapy for MI has been under investigation for more than a decade, there still has not been a consensus over the identity of the adult endogenous CSC. Recent clinical trials, using selected Ckit+ cells or the cardiosphere-derived cells (CDCs) have shown moderate results. The aim of this thesis was to develop a digestion-based method for isolation of cardiac progenitor cells (CPCs) from the mouse atria. The resulting "CTs" were isolated by collagenase/trypsin (where their name has resulted from) digestion with a prolonged period step for cell attachment. CTs were compared to isolated CDCs for their marker expression, using RT-PCR and Immunocytochemistry, showing cells with a mesenchymal phenotype which expressed SCA1 and CKIT. The CDCs had more of a fibroblast phenotype with higher Ddr2 and Wt1 expression. Using a TGF-β1 differentiation protocol, the CTs could be differentiated more effectively to a CM lineage than could the CDCs. In addition, Oleic acid (OA) supplementation stimulated the Peroxisome proliferator-activated receptor alpha pathway and led to maturation of the CT cells, both before and after differentiation. The differentiated CTs begin to express Tnnt2, while OA led to Myh7 increase and upregulated their oxidative metabolism. Finally, the CTs were more able to survive under serum-starvation than the CDCs, and transfection with miR-210 could enhance CT survival under these conditions and increased VEGF secretion. By digestion of the whole atria and allowing a prolonged time for attachment, we have developed a novel isolation protocol which generates a cell population containing a range of progenitors. Cells within this population can survive under serum starvation and can be differentiated to a CM lineage, making them a promising therapeutic population.