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1
Islam, Azharul. "Cell-walls of growing plant cells." Thesis, University of Westminster, 2013. https://westminsterresearch.westminster.ac.uk/item/8z033/cell-walls-of-growing-plant-cells.
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The plant primary cell wall is a three-dimensional interwoven network of cellulose microfibrils, cross-linked by xyloglucan and dispersed in a pectin matrix. It has been suggested that in the wall of growing plant cells, xyloglucan is bound to the rigid cellulose microfibrils by hydrogen bonds and holds the microfibrils together by forming molecular tethers, which is referred to as the ‘sticky network’ model. Plant growth occurs when these tethers are peeled from the microfibrils by expansins or broken by glycosidases or transglycosylases. A number of researchers have presented theoretical difficulties and observations inconsistent with this model and a new hypothesis has been proposed, claiming that the cellulose – xyloglucan cross-links may act as ‘scaffolds’ holding the microfibrils apart. Analogies with synthetic polymers suggests that the spacing between the cellulose microfibrils may be an important determinant of the mechanical properties of the cell wall and the results presented in this thesis support this hypothesis. Water contents of Acetobacter xylinus synthesized cellulose based cell wall analogues (as a mimic of primary cell wall) and sunflower hypocotyl cell walls were altered using high molecular weight polyethylene glycol (PEG) solution, and their extension under a constant load was measured using a creep extensiometer and showed that there were clear reduction (30-35%) in extensibility suggesting that water content of the wall and therefore the cell wall free volume directly influence wall extensibility. When hydration of A. xylinus cellulose composite pellicles was reduced using PEG 6000 solution and re-hydrated in buffer solution, followed by treatment with α-expansin or snail acetone powder extract, it was found that expansin and snail powder extracts caused a rapid rehydration of the composites and that the pellicles only returned to their original weights after these treatments, suggesting that expansin and snail powder can increase the free volume of the wall perhaps contributing to the increases in extensibility that they cause. Assays on cell wall fragments also indicated that expansin increased the cell wall free volume, demonstrated by changes of the turbidity of fragment suspensions. The role of pectic polysaccharide, RG-II, in cell wall biomechanics was also investigated using mechanical and biochemical testing of available Arabidopsis thaliana cell wall mutants and by incorporating RG-II (purified from red wine) with Acetobacter cellulose. It was demonstrated that RG-II significantly increased the hydration of cellulose composite; hydration rate was 15 -16% more than the composite without RG-II and thus increased the pellicle extensibility. From the results, it is evidenced that cell wall extension is not only the consequences of breaking hydrogen bonds between cellulose microfibrils and xyloglucan by expansins or glycosidases and transglycosylases, but also a wider range of factors are involved including cell wall water content, cell wall free volume and the pectic polymers, especially RG-II.
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Koreeda, Satoshi. "Basal cell carcinoma cells resemble follicular matrix cells rather than follicular bulge cells." Kyoto University, 2004. http://hdl.handle.net/2433/147556.
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Leskinen, Markus. "Mast cell-mediated apoptosis of smooth muscle cells and endothelial cells." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/leskinen/.
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Carnathan, Diane Gail Vilen Barbara J. "Dendritic cell regulation of B cells." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1200.
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Thesis (M.S.)--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 Master of Science in the Department of Microbiology and Immunology, School of Medicine." Discipline: Microbiology and Immunology; Department/School: Medicine.
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Iqbal, Syed Amir. "Asymmetric Cell Division in Mammalian Cells." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.503635.
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Cadart, Clotilde. "Cell size homeostasis in animal cells." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS103/document.
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Le mécanisme d’homéostasie de taille chez les cellules animales est très peu compris actuellement. Cette question est pourtant d’un intérêt majeur car le maintien de l’homéostasie de taille dans une population de cellules prolifératives doit se faire par une coordination entre la croissance et la division. Chez la levure S. pombe, il a ainsi été montré que la taille est une information cruciale pour déclencher l’entrée en mitose (Fantes, 1977). Chez plusieurs bactéries et les cellules filles de la levure S. cerevisiae au contraire, de récentes études ont au contraire montré que l’homéostasie de taille était le résultat d’une addition constante de volume, indépendamment de la taille initiale des cellules (Campos et al., 2014; Soifer et al., 2016; Taheri-Araghi et al., 2015). Ce mécanisme est appelé « adder » et génère une régression des tailles à la moyenne, génération après génération. Ces résultats ont été possibles grâce au développement de techniques permettant la mesure dynamique du volume à l’échelle de la cellule unique et sur plusieurs générations. Une telle mesure est cependant très difficile chez les cellules de mammifère dont le volume fluctue constamment et qui cyclent sur des temps plus longs (environ 20 heures). Pour cette raison, la plupart des approches proposées sont indirectes (Kafri et al., 2013; Sung et al., 2013; Tzur et al., 2009) ou reposent sur une mesure de la masse plutôt que du volume (Mir et al. 2014; Son et al., 2012). Ensemble, ces études ont montré que les cellules de mammifère croissaient de manière exponentielle. Elles ont aussi remis en cause le modèle traditionnel qui proposait que l’homéostasie de taille reposait sur l’adaptation de la durée du cycle et mis en avant un rôle de la régulation de la vitesse de croissance. Cependant, aucun modèle n’a réellement été proposé ou démontré. La nature et l’existence même d’un mécanisme maintenant l’homéostasie de taille des cellules de mammifère est en fait discutée (Lloyd, 2013).Pour caractériser l’homéostasie de taille des cellules de mammifères, nous avons développé une technique permettant pour la première fois la mesure du volume de ces cellules sur des cycles complets (Cadart et al., 2017; Zlotek-Zlotkiewicz et al. 2015). Nous montrons que plusieurs types cellulaires (HT29, MDCK et HeLa) se comportent d’une manière similaire à celle d’un « adder ». Pour tester davantage cette observation, nous induisons artificiellement des divisions asymétriques en confinant les cellules dans des micro-canaux. Nous observons que les asymétries de tailles sont réduites mais pas complètement corrigées au cours du cycle suivant, à la manière d’un « adder ». Pour comprendre comment la croissance et la progression dans le cycle sont coordonnées et génère cet « adder », nous combinons notre méthode de mesure de volume avec un suivi de la progression dans les différentes phases du cycle. Nous montrons que la durée de la phase G1 est inversement corrélée au volume initial des cellules. Cependant, cette corrélation semble contrainte par une durée minimale de G1 mise en évidence lors de l’étude de cellules artificiellement poussées à atteindre de grandes tailles. Néanmoins, même dans cette condition où la modulation de la durée du cycle est perdue, l’observation du « adder » est maintenue. Ceci suggère un rôle complémentaire de la régulation de la vitesse de croissance des cellules. Nous proposons donc une méthode pour estimer théoriquement la contribution relative de l’adaptation de la vitesse de croissance et de la durée du cycle dans le contrôle de la taille. Nous utilisons cette méthode pour proposer un cadre général où comparer le processus homéostatique des bactéries et de nos cellules. En conclusion, notre travail apporte pour la première fois la démonstration que les cellules de mammifères maintiennent l’homéostasie grâce à un mécanisme similaire au « adder ». Ce mécanisme semble impliquer à la fois une modulation de la durée du cycle et du taux de croissanceThe way proliferating mammalian cells maintain a constant size through generations is still unknown. This question is however central because size homeostasis is thought to occur through the coordination of growth and cell cycle progression. In the yeast S. pombe for example, the trigger for cell division is the reach of a target size (Fantes, 1977). This mechanism is referred to as ‘sizer’. The homeostatic behavior of bacteria and daughter cells of the yeast S. cerevisiae on the contrary was recently characterized as an ‘adder’ where all cells grow by the same absolute amount of volume at each cell cycle. This leads to a passive regression towards the mean generation after generation (Campos et al., 2014; Soifer et al., 2016; Taheri-Araghi et al., 2015). These findings were made possible by the development of new technologies enabling direct and dynamic measurement of volume over full cell cycle trajectories. Such measurement is extremely challenging in mammalian cells whose shape constantly fluctuate over time and cycle over 20 hours long periods. Studies therefore privileged indirect approaches (Kafri et al., 2013; Sung et al., 2013; Tzur et al., 2009) or indirect measurement of cell mass rather than cell volume (Mir et al. 2014; Son et al., 2012). These studies showed that cells overall grew exponentially and challenged the classical view that cell cycle duration was adapted to size and instead proposed a role for growth rate regulation. To date however, no clear model was reached. In fact, the nature and even the existence of the size homeostasis behavior of mammalian cells is still debated (Lloyd, 2013).In order to characterize the homeostatic process of mammalian cells, we developed a technique that enable measuring, for the first time, single cell volume over full cell cycle trajectories (Cadart et al., 2017; Zlotek-Zlotkiewicz et al. 2015). We found that several cell types, HT29, HeLa and MDCK cells behaved in an adder-like manner. To further test the existence of homeostasis, we artificially induced asymmetrical divisions through confinement in micro-channels. We observed that asymmetries of sizes were reduced within the following cell cycle through an ‘adder’-like behavior. To then understand how growth and cell cycle progression were coordinated in way that generates the ‘adder’, we combined our volume measurement method with cell cycle tracking. We showed that G1 phase duration is negatively correlated with initial size. This adaptation is however limited by a minimum duration of G1, unraveled by the study of artificially-induced very large cells. Nevertheless, the adder behavior is maintained even in the absence of time modulation, thus suggesting a complementary growth regulatory mechanism. Finally, we propose a method to estimate theoretically the relative contribution of growth and timing modulation in the overall size control and use this framework to compare our results with that of bacteria. Overall, our work provides the first evidence that proliferating mammalian cells behave in an adder-like manner and suggests that both growth and cell cycle duration are involved in size control
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BARBERI, CHIARA. "Myeloma cells induce the accumulation of activated CD94low NK cells by cell-to-cell contacts involving CD56 molecules." Doctoral thesis, Università degli studi di Genova, 2020. http://hdl.handle.net/11567/996094.
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Natural Killer (NK) cells represent innate effector cells potentially able to play a role during the immune response against Multiple Myeloma (MM). To better define the distribution and the specific properties of NK cell subsets during MM disease, we analyzed their features in the bone marrow and peripheral blood of newly diagnosed MM patients. Our findings revealed that, in both compartments, NK cells were more abundant than in healthy donors. Among total MM-NK cells, a significant increase of CD94lowCD56dim NK cell subset was observed, which already appears in clinical precursor conditions leading to MM, namely monoclonal gammopathy of undetermined significance and smoldering MM, and eventually accumulates with disease progression. Moreover, a consistent fraction of CD94lowCD56dim NK cells was in a proliferation phase. When analyzed for their killing abilities, they represented the main cytotoxic NK cell subset against autologous MM cells. In vitro, MM cells could rapidly induce the expansion of the CD94lowCD56dim NK cells subset, thus reminiscent of that observed in MM patients. Mechanistically, this accumulation relied on cell to cell contacts between MM and NK cells and required both activation via DNAM-1 and homophilic interaction with CD56 expressed on MM cells. Considering the growing variety of combination treatments aimed at enhancing NK cell-mediated cytotoxicity against MM, these results may also be informative for optimizing current immunotherapeutic approaches.
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Liu, Hao. "Dendritic cell development directed by stromal cells." Thesis, University of York, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516409.
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Crawford, A. "How B cells influence T cell responses." Thesis, University of Edinburgh, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.645118.
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Although studies using B cell deficient mice have been useful in understanding the importance of B cells under different conditions, it is difficult to then dissect exactly how B cells could be regulating T cell responses. By transferring OT-II transgenic T cells into either B cell deficient (μMT) or C57BL/6 mice, expansion and contraction of T cells can be tracked ex vivo. Expansion of OT-II cells is reduced in μMT mice compared to C57BL/6 mice. Thus, B cells can provide costimulatory signals, secrete cytokines and influence the lymphoid microarchitecture. To dissect which B cell factor(s) are involved in enhancing OT-II T cell expansion, a model system was used where one molecule on the B cells is depleted at one time. This was achieved by creating bone-marrow chimeras using a combination of μMT bone-marrow and wildtype or deficient bone-marrow. Thus, all the B cells are either wildtype or deficient for a particular molecule. The molecules examined were MHC-II, which is required for antigen presentation, CD40, due to its costimulatory role, and lymphotoxin-alpha, for its role in maintenance of splenic architecture. Using the OT-II adoptive transfer system, we have shown a requirement for MHC-II but not CD40 on B cells for efficient T cell expansion. In light of these observations, the role of B cell-derived MHC-II for T cell memory generation was examined. To do this, I used MHC-II tetramers to track a polyclonal population of T cells in the host. Using this technique, I have shown that T cell memory is also diminished when the B cells do not express MHC-II. Thus, a cognate interaction with B cells is required for both efficient expansion and memory generation of CD4+ T cells.
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El-Sherbiny, Yasser Mohamed. "Natural killer cells and plasma cell neoplasia." Thesis, University of Leeds, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438481.
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Worapamorn, Wilairat. "Cell-surface proteoglycan expression by periodontal cells /." St. Lucia, Qld, 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16097.pdf.
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Nie, Yingjie. "Defective dendritic cells and mesenchymal stromal cells in systemic lupus erythematosus and the potential of mesenchymal stromal cells as cell-therapy." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43278681.
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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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Gale, Zoe. "Glial cell line-derived neurotrophic factor effects on dental pulp cells and osteoblast-like cells." Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3268/.
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Glial cell line-derived neurotrophic factor (GDNF) is a growth factor promoting survival, proliferation and differentiation of neural crest cells. Neural crest cells play an important role within mesenchymal tissues during dental pulp and calvarial bone development. GDNF also has a role within non-neuronal tissues and is expressed during dental development. GDNF null mutations prevent the formation of the mineralised hard tissues of the tooth. The hypothesis for this study was that GDNF affects mesenchymal dental pulp cells (DPC), promoting the regenerative responses of mineralised tissues. This study utilised cell culture models to investigate the direct effects of GDNF on the proliferation and differentiation of dental pulp cells, bone marrow mesenchymal stromal/stem cells (BMSC) and calvarial osteoblasts. This research demonstrated that these culture models expressed GDNF and its receptors GFR\(\alpha\)1 and RET. GDNF was shown to directly stimulate DPC and osteoblast-like cell proliferation and differentiation. Moreover, GDNF was cytoprotective when DPCs were cultured under conditions reflecting aspects of inflammation, which may occur during repair. These conditions included supplementation with the pro-inflammatory cytokine TNF\(\alpha\) and culture under serum-starved conditions. It is proposed that GDNF may play an important regulatory role in dental pulp homeostasis and bone metabolism.
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Tabayoyong, William Borj. "Engraftment of embryonic stem cell-derived hematopoietic progenitor cells is regulated by natural killer cells." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/1089.
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Embryonic stem (ES) cells possess the remarkable ability to form cells and tissues from all three germ layers, a characteristic known as pluripotency. In particular, the generation of ES cell-derived hematopoietic cells could serve as an alternate source of hematopoietic stem cells for transplantation in place of bone marrow cells, which are limited by donor availability and high immunogenicity. The advantages of ES cell-derived hematopoietic cells over bone marrow cells include a greater proliferative capacity, which alleviates the problems of donor shortage, and low level expression of MHC antigens, which suggests immune privilege. However, it is unclear whether the immune system is capable of recognizing and rejecting ES cell-derived hematopoietic cells following transplantation. The observation that ES cell-derivatives express low levels of MHC class I, the predominant inhibitory ligand for NK cells, led us to hypothesize that ES cell-derived hematopoietic progenitor cells (HPC) are susceptible to NK cell-mediated killing.
To test this hypothesis, we first generated HPCs from murine ES cells ectopically expressing HOXB4, a homeobox transcription factor that confers hematopoietic self-renewal, and confirmed that HPCs expressed low levels of MHC class I antigens. To specifically investigate the role of NK cells in regulating the in vivo engraftment of HPCs, we transplanted NK-replete Rag2-/- or NK-deficient Rag2-/-γc-/- mice with HPCs. We observed permanent HPC engraftment in Rag2-/-γc-/- mice; however, HPC engraftment was significantly reduced in Rag2-/- mice and was eventually eliminated over time. Bone marrow harvested from these animals showed that HPC-derived Lin-c-kit+ and Lin-Sca-1+ progenitor cells, critical progenitor cells for long-term hematopoietic engraftment, were deleted in Rag2-/- but not in Rag2-/-γc-/- mice.
Next, we focused on the mechanism of NK cell activation by HPCs. Increased expression of the cytotoxic proteins Granzyme B and Perforin in the NK cells of HPC-transplanted Rag2-/- mice confirmed in vivo NK cell activation. Phenotypic analysis of HPCs revealed high level expression of H60, a ligand of the NK activating receptor NKG2D, and neutralization of H60 rescued HPCs from NK cell-mediated killing.
Altogether, our results demonstrate that NK cells are a major barrier to the successful engraftment of ES cell-derived hematopoietic cells, underlining an important role of the innate immune system in regulating the long-term engraftment of ES cell derivatives.
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Hou, Yuen-chi Denise. "A comparative study on the effects of feeder cells on culture of human embryonic stem cells." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43703604.
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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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Meletis, Konstantinos. "Studies on adult stem cells /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-803-7/.
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Rabodzey, Aleksandr. "Flow-induced mechanotransduction in cell-cell junctions of endothelial cells." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/41586.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2006.Includes bibliographical references (leaves 86-92).
Endothelial cells show an unexpected behavior shortly after the onset of laminar flow: their crawling speed decreases ~40% within the first 30 min, but only in a confluent monolayer of endothelial cells, not in subconfluent cultures, where cell-cell interactions are limited. This led us to study early shear effects on cell-cell adherens junctions. We found a 30±6% increase in the number of VE-cadherin molecules in the junctions. The strength of interactions of endothelial cells with surfaces coated with recombinant VE-cadherin protein also increased after laminar flow. These observations suggest that endothelial cell junction proteins respond to flow onset. The process of clustering may induce diffusion of monomers to the junction area, resulting in an overall increase in VE-cadherins in the junctions. To directly confirm the role of adherens junctions in the decrease in cell crawling speed, we used siRNA-knockdown technique to produce cells lacking VE-cadherin. These cells showed no decline in crawling speed under flow. Our interpretation is consistent with previous data on junction disassembly 8 hr after flow onset. The speed of endothelial cell crawling returns to the original level by that time, and junctional disassembly may explain that phenomenon. In order to understand better the change in VE-cadherin distribution under flow and during junction formation and remodelling, we developed a mathematical model of VE-cadherin redistribution in endothelial cells. This model allowed us to develop a quantitative framework for analysis of VE-cadherin redistribution and estimate the amount of protein in the junctions and on the apical surface. In addition to that, the model explains rapid junction disassembly in the leukocyte transmigration and junction formation in subconfluent cells.
(cont.) These studies show that intercellular adhesion molecules are important in the force transmission and shear stress response. Their role, however, is not limited to flow mechanotransduction. Intercellular force transmission has an important application - organ development and, specifically, angiogenesis. We studied the role of VE-cadherin in vessel development in HUVECs and showed that VE-cadherin-null cells do not form vessels in the in vitro assay. This observation confirms the important role of intercellular force transmission in response to external force caused by flow or exerted by other cells.
by Aleksandr Rabodzey.
Ph.D.
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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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Joseph, Krishna Sathyamurthy. "Hybrid direct methanol fuel cells." Thesis, Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/44777.
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A new type of fuel cell that combines the advantages of a proton exchange membrane fuel cells and anion exchange membrane fuel cells operated with methanol is demonstrated. Two configurations: one with a high pH anode and low pH cathode (anode hybrid fuel cell (AHFC)),and another with a high pH cathode and a low pH anode (cathode hybrid fuel cell (CHFC)) have been studied in this work. The principle of operation of the hybrid fuel cells were explained. The two different hybrid cell configurations were used in order to study the effect of the electrode fabrication on fuel cell performance. Further, the ionomer content and properties such as the ion exchange capacity and molecular weight were optimized for the best performance. A comparison of the different ionomers with similar properties is carried out in order to obtain the best possible ionomer for the fuel cell. An initial voltage drop was observed at low current density in the AHFC, this was attributed to the alkaline anode and the effect of the ionomers with the new cationic groups were studied on this voltage drop was studied. These ionomers with the different cationic groups were studied in the CHFC design as well. Finally, the use of non platinum catalyst cathode with the CHFC design was also demonstrated for the first time.
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Hou, Yuen-chi Denise, and 侯元琪. "A comparative study on the effects of feeder cells on culture of human embryonic stem cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hdl.handle.net/10722/210317.
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Egawa, Haruto. "Peripheral blood mononuclear cells in early pregnancy promote invasion of human choriocarcinoma cell line, BeWo cells." Kyoto University, 2004. http://hdl.handle.net/2433/147458.
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Clayton, Zoe Ellen. "The pro-angiogenic properties of induced pluripotent stem cell derived endothelial cells and induced endothelial cells." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/17300.
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Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, (1, 2). Current interventions are ineffective in up to 30% of patients due to the presence of diffuse or extensive atherosclerosis, therefore the development of alternative or supplementary therapies for CVD is a high priority for medical research. Therapeutic angiogenesis, enhancing the growth of new blood vessel networks from the existing vasculature, is a promising strategy for restoring blood flow to ischaemic tissue. Stem cells have shown potential as pro-angiogenic therapies for patients with coronary artery disease (CAD) and peripheral artery disease (PAD). Induced pluripotent stem cells (iPSCs) can be derived from plentiful sources of adult somatic cells, such as dermal fibroblasts (3, 4). Human iPSCs have been differentiated to endothelial cells (iPSC-ECs) and, more recently, induced endothelial cells (iECs) have been generated by direct differentiation of fibroblasts, which bypasses the pluripotent intermediate (5-11). IPSC-ECs and iECs have potential advantages over other cell types in that they can be generated in large quantities, they are not of embryonic origin and they have minimal immunogenicity. Endothelial cells have been produced via many different reprogramming and differentiation protocols, but little work has been done to determine which of these methods generates populations of cells with the greatest therapeutic potential. The studies presented in this thesis show that both iPSC-ECs and iECs have endothelial functionality in vitro and can enhance ischaemia mediated angiogenesis in a murine model of PAD. Our findings suggest that iPSC-ECs may be the more robust cell type as they demonstrate superior survival and engraftment potential in vivo. We have also generated novel data showing that iPSC-ECs enhance wound perfusion, increase wound collagen content and accelerate wound closure, which suggests they are a promising candidate therapy for chronic wounds and diabetic ulcers. Overall, the work presented in this thesis provides evidence to support the development of clinical-grade iPSC-ECs and iECs for therapeutic angiogenesis in cardiovascular disease settings.
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Aarum, Johan. "Interactions between mouse CNS cells: microglia and neural precursor cells /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-120-2/.
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Gustavsson, Natalia. "Cell-Specific Ca2+ Response in Pancreatic ß-cells." Doctoral thesis, Umeå universitet, Histologi med cellbiologi, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-661.
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Pancreatic ß-cells are heterogeneous in their secretory responsiveness, glucose sensitivity and metabolic rate. A diminished and delayed first-phase insulin release is an early sign of failing ß-cells in diabetes. Mechanisms controlling functional characteristics, such as lag time for insulin release or magnitude of the response in each individual cell are unknown. To find out whether the heterogeneity represents a random phenomenon in ß-cell or is a manifestation of reproducible characteristics, we compared parameters of Ca2+ response in Fura-2 labelled ob/ob mouse ß-cells during two consecutive stimulations with glucose. Lag times, as well as peak heights and nadirs of initial lowering showed a strong correlation between the first and second stimulation. Thus, timing and magnitude of the early Ca2+ response were specific for each cell. ß-Cells from lean mice, diabetic db/db mice and rats also showed cell-specific responses characteristics. This indicates that a cell-specific Ca2+ response to glucose is common in rodent ß-cells, both normal and diabetic. Another question was whether aggregated ß-cells show cell-specific responses. Using the same protocol as for dispersed ß-cells, we analysed Ca2+ responses in clusters of different size and in intact islets from ob/ob and lean mice. Correlations were found between the first and second stimulation for timing and magnitude of [Ca2+]i rise, and for the initial lowering. Next, we tested if the ß-cell response is cell-specific, when induced at different steps of the stimulus-secretion coupling. The glycolytic intermediate glyceraldehyde, the mitochondrial substrate KIC, the KATP-channel blocker tolbutamide and arginine were used as tools. [Ca2+]i changes were studied in dispersed ß-cells from lean, ob/ob and db/db mice. NADH responses to glucose and KIC were analyzed as a measure of metabolic flux. The correlation between Ca2+ and insulin response from individual ß-cells was tested using Fluo-3 and Fluozin-3. Both timing and magnitude of calcium responses were cell-specific in lean mouse ß-cells with all tested secretagogues. ß-Cells from ob/ob and db/db mice showed cell-specific timing of Ca2+ responses to glyceraldehyde but not to KIC, tolbutamide or arginine. However, ob/ob mouse ß-cells within intact islets showed cell-specific timing of tolbutamide-induced response. NADH responses to glucose were cell-specific in all three mouse models, but the timing of NADH responses to KIC was cell-specific only in lean mice. Thus, a cell-specific response can be induced in normal ß-cells at several steps of stimulus-secretion coupling for nutrient-stimulated insulin release. Cell-specific properties of ß-cell ion channels and the mitochondrial metabolism are affected in db/db and ob/ob mice. The relation between mitochondrial mass and parameters of Ca2+ responses were investigated in Mitotracker Red and Fluo-3 labelled ß-cells using confocal microscopy. Data show that ß-cell mitochondrial state may play an important role in determining the timing of [Ca2+]i changes. In summary, the early Ca2+ response pattern in ß-cells, including the lag time, the nadir of initial lowering and the height of the first peak response is cell-specific. Isolated and functionally coupled ß-cells show cell-specific timing of Ca2+ responses when stimulated with metabolic and non-metabolic agents. This may be a robust mechanism of importance for the adequate function of ß-cells and a basis for the pacemaker function of some cells. A disturbed cell specificity of the mitochondrial metabolism and ion channel function appears to be a marker of ß-cell dysfunction in hyperglycemia and diabetes and may explain the delayed insulin release in ß-cells from diabetic subjects.
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Liu, Qing. "Curcumin induces cell inhibition in breast cancer cells." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B38688608.
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Chisholm, S. E. "Natural killer cell recognition of virally infected cells." Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597615.
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Natural killer (NK) cells are known to be important for the control of viral infections, particularly infection with large double stranded (ds)DNA viruses such as herpes simplex virus type 1 (HSV-1) and vaccinia virus (VV), but the pathways and interactions important for NK cell recognition of virally infected cells are not well understood. Thus, the aim of this thesis was to study the molecular mechanisms of NK cell recognition of target cells infected with either HSV-1 or VV. Experiments using a set of HSV-1 mutants, deficient in one or more of the immediate early (IE) genes, demonstrated that expression of ICP0 alone was found to be sufficient to render HSV-1 infected target cells susceptible to NK attack, and killing assays demonstrated that the natural cytotoxicity receptors (NCRs) were involved in the NK mediated killing of HSV-1 infected targets. For VV, it was not possible to narrow down exactly which VV gene was sufficient for generating NK cell mediated susceptibility, but the data indicated that the VV gene or genes involved are expressed early, conserved within the poxvirus family, and as such, likely to be essential for the virus. Flow cytometry experiments demonstrated that altered susceptibility of the target cells to NK cell lysis was due to upregulation of ligands for the NCRs, and the importance of the NCRs in NK mediated killing of VV infected targets was confirmed by killing assays. In addition, flow cytometry experiments demonstrated very little down regulation of MHC class I followed infection by either HSV-1 or VV, implying that MHC class I down regulation is not of major importance in NK mediated killing of infected cells.
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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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Liu, Qing, and 劉晴. "Curcumin induces cell inhibition in breast cancer cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B38688608.
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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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Snell, Daniel C. "Cell-surface molecules of developing chicken B cells." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326977.
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Mahajan, Simmi. "Development of T cell help for B cells." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/12548.
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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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Wang, Qiufan Claire, and 王秋帆. "Mechanisms of junctional restructuring at the sertoli-sertoli and sertoli-germ cell interfaces during spermatogenesis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40887686.
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Wang, Qiufan Claire. "Mechanisms of junctional restructuring at the sertoli-sertoli and sertoli-germ cell interfaces during spermatogenesis." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B40887686.
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Wu, Yue. "Generating Beta-cells from liver cells." Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420423.
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Chowdhury, Azazul Islam. "Role of Cell-cell Interactions and Palmitate on β-cells Function." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk cellbiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-230841.
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The islets of Langerhans secrets insulin in response to fluctuations of blood glucose level and efficient secretion requires extensive intra-islet communication. Secretory failure from islets is one of the hallmark in progression of type 2 diabetes. Changes in islet structure and high levels of saturated free fatty acids may contribute to this failure. The aim of this thesis is to study the role of cell-cell interactions and palmitate on β-cells functions. To address the role of cell-cell interactions on β-cells functions MIN6 cells were cultured as monolayers and as pseudoislets. Glucose stimulated insulin secretion was higher in pseudoislets compared to monolayers. Transcript levels of mitochondrial metabolism as well glucose oxidation rate was higher in pseudoislets. Insulin receptor substrate-1 (IRS-1) phosphorylation was altered when cells were grown as pseudoislets. Proteins expression levels related to glycolysis, cellular connections and translational regulations were up-regulated in pseudoislets. We propose the superior capacity of pseudoislets compared to monolayers depend on metabolism, cell coupling, gene translation, protein turnover and differential IRS-1 phosphorylation. To address the role of palmitate on β-cells human islets were cultured in palmitate. Long term palmitate treatment decreased insulin secretion which is associated with up-regulation of suppressor of cytokine signaling-2 (SOCS2) and protein inhibitor of activated STAT-1 (PIAS1). Up-regulation of SOCS2 decreased phosphorylation of Akt at site T308, whereas PIAS1 decreased protein level of ATP- citrate lyase (ACLY) and ATP synthase subunit B (ATP5B). We propose long term palmitate treatment reduces phosphatidylinositol 3-kinase (PI3K) activity, attenuates formation of acetyl-CoA and decreases ATP synthesis which may aggravate β-cells dysfunction.
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Wang, Wei. "Modulation of immune cell responses by small cell lung cancer cells." Thesis, King's College London (University of London), 2016. https://kclpure.kcl.ac.uk/portal/en/theses/modulation-of-immune-cell-responses-by-small-cell-lung-cancer-cells(7bdc85c2-acd8-4f13-9d2b-e2ce07d1567b).html.
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Small Cell Lung Cancer (SCLC) accounts for 15-20% of all lung cancers and kills at least one person every 2 hours in the UK. There is no effective treatment and overall 2-year survival is less than 5%. Patients with SCLC have poorly understood local and systemic immune defects. Previous studies have shown several important defects in cell-mediated immune responses in patients with SCLC. A better understanding of interactions between SCLC tumour cells and immune cells may lead to the development of novel therapeutic approaches. There is increasing recognition that immunological biomarkers may add to traditional histological analyses and can be exploited in the management of multiple epithelial malignancies. There are currently no such markers used in the management of SCLC. In my PhD project, I have shown that cell lines from different SCLC patients have differential immunosuppressive capabilities. These properties are mediated by the secretion of differing levels of soluble molecules that can suppress the mixed leukocyte reaction (MLR) and CD4+ T cell proliferation, induce IL-10 secretion and differentiation of functional CD4+CD25+CD127+FoxP3+Helios- regulatory T cells (Tregs) from naïve CD4+ T cells. IL-15 is secreted by SCLC cells in culture in proportion to their immunosuppressive capability. Its in vivo relevance is supported by its presence in tumour biopsy samples. The suppressive effect on CD4+ T cell proliferation and the induction of Treg cell population was not affected by blocking IL-10 or TGF-β signalling but was partially reversed by blocking IL-15 activity. Therefore, IL-15 is one, though not the only, soluble molecule produced by SCLC cells to mediate immune suppression by inducing increased population of Treg cells. This may represent a mechanism by which SCLC cells can suppress the immune response. In addition, SCLC cells supressed TNF-α release from monocytes in response to LPS stimulation, down-regulated expression of CD16 and CD86 and upregulated expression of CD163 and CD206 on monocyte-derived macrophages (MDMs) upon activation. This M2-like phenotype poralization was associated with decreased TNF-α and IL-6 production and increased IL-10 secretion. These effects were abrogated by blocking the signalling of bombesin-like peptides (BLPs) that are neuropeptides produced by SCLC cells using a GRP receptor (GRP-R) antagonist. Therefore, the polarization of macrophages to an M2-like phenotype by SCLC cell-derived BLPs may represent another mechanism by which SCLC tumours suppress the immune response. Finally, SCLC tumour biopsies were shown to be infiltrated with various mononuclear immune cells and Treg cells. CD45 and FoxP3 were used as paninflammatory cell and Treg cell markers respectively. An elevated CD45+ infiltrate was predictive of prolonged survival in SCLC independent of age, sex, stage or treatment strategy. An elevated FoxP3+/CD45+ ratio was predictive of a significantly worse prognosis. This study identifies potential mechanisms by which SCLC tumour cells may downregulate local and systemic immune response, and also identifies an independent prognostic marker to predict patient survival in SCLC. Further, IL- 15 and BLPs are potential novel therapeutic targets in SCLC.
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Murray, Nicholas. "Costimulation of T cells and its role in T cell recognition of malignant colorectal cells in vitro." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301247.
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Wang, Yenfeng. "The role of mast cells in foam cell formation, growth inhibition, and apoptosis of smooth muscle cells." Helsinki : University of Helsinki, 1999. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/wang/.
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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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Huynh, The Hung. "Establishment of bovine mammary epithelial cell lines : an in vitro model for lactation." Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=60426.
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Clonal cell lines were isolated from mammary gland tissue epithelial cell cultures of lactating cows. Early passage clonal bovine mammary epithelial cells (clone LMH17) gave rise to several established cell lines (MAC-T lines) after being cotransfected with plasmids containing the temperature sensitive mutant SV40 large T antigen gene (pBAPSV40TtsA58) and the bacterial phosphotransferase gene (pSV2-neo). Unlike other cell types which were transformed after being transfected with SV40, MAC-T cells maintained many characteristics of non-transformed cells: MAC-T cells were serum and anchorage dependent, showed contact inhibition, and were not tumorigenic in immunodeficient mice. However, Southern transfer analysis revealed an integrated SV40 gene and cells showed no senescence after 50 passages. These cells are morphologically indistinguishable from parental LMH17 cells and retain the typical morphology of mammary epithelial cells. Positive cytokeratin immunostaining and the absence of vimentin staining indicated that these cells were epithelial in origin.MAC-T cells grew rapidly on plastic substratum with a doubling time of approximately 17 hours and became differentiated when grown on floating collagen gels in the presence of prolactin. The differentiated phenotype was characterized to include (1) the ability to form secretory domes with a lumen from a pavement of columnar cells; (2) increased casein mRNA abundance; (3) increased alpha S and beta casein secretion; (4) increased number and size of casein secretory vesicles; and (5) increased lactose synthesis and secretion.
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Offiah, I. "Cross-talk between human T cells, mast cells and conjunctival epithelial cells." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1348498/.
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The ocular surface is continually exposed to the outside environment and is a common site of inflammation. Conjunctival epithelial cells are thought to play a role in innate responses at the ocular surface. The hypothesis of my study is that conjunctival epithelial cells also contribute to T cell and mast cell effector mechanisms in chronic allergic eye disease via secretion of cytokines. In this study we initially demonstrate that the conjunctiva expresses TLRs, and that the TLR3 ligand (poly I:C) activates conjunctival epithelial cells in vitro to secrete inflammatory mediators as part of the innate immune response. Conjunctival tissues were also shown to express the Th2 associated cytokine, IL-13 as well as TSLP – a cytokine thought to be involved in Th2 differentiation. Conjunctival tissues from chronic allergic eye disease subjects were found to have increased IL-13 and TSLP expression compared to normal controls. Using a human conjunctival epithelial cell line, cells could be induced to express increased levels of TSLP following exposure to poly I:C or pro-inflammatory cytokines. Th17 cells, identified by coexpression of CD4 and IL-17, were also detected in CAED tissues and a high level of expression of IL-17A was localised to the epithelium. However, although capable of secreting IL- 25, IL-17A was not secreted by conjunctival epithelial cells, indicating that the IL-17 observed histologically may have been IL-17 binding to the surface of the epithelium. IL-17 receptor C (IL-17RC) expression was found to be increased in CAED tissues whilst IL-17RA was upregulated when conjunctival epithelial cells were stimulated with pro-inflammatory cytokines together with poly I:C. Blockade of IL-17RA and subsequent stimulation with IL-17 led to increased IL-8 and decreased TGF-β secretion. Although being implicated in the immunopathogenesis of certain diseases, IL-17 and its other family members may potentially serve to play an immunoregulatory role in immunity at the ocular surface.
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Vasu, Srividya. "Molecular mechanisms of toxicity and cell damage in clonal human and mouse pancreatic beta cells, alpha cells, and intestinal L cells exposed to diabetic milieu." Thesis, Ulster University, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.646400.
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Novel human pancreatic beta cell line, 1.IB4 was generated only recently by electrofusion of human islet cells and immortal P ANC-I cell line. In contrast, the mouse insulinoma cell line - MIN6, pancreatic alpha cell line - Alpha TCI clone 9 and GLP-I secreting enteroendocrine cell line - GLUTag are widely used in diabetes research. While cellular responses of pancreatic beta cells on exposure to diabetic conditions have been studied extensively, responses of this novel human insulin secreting cell line and pancreatic alpha and intestinal L cells have not been evaluated previously. In this thesis, mechanisms of toxicity and cell damage in 1.1B4, MIN6, Alpha TCI clone 9 and GLUTag cells exposed t9 diabetic milieu were evaluated. 1.1B4, MIN6 and GLUTag cells suffered cell death on exposure to chemicals, high glucose, palmitate and cytokines while Alpha TCI clone 9 cells were relatively resistant to these agents. 1.lB4 and MIN6 cell secretory function, insulin content and mRNA expression of genes involved in stimulus secretion coupling were affected to differing degrees. Expression of antioxidant enzyme genes was upregulated but was insufficient to detoxify ROS generated by toxins with the exception of Alpha TCI clone 9 cells. Pro-inflammatory cytokines caused nitrosative stress while other toxins caused oxidative stress, which was evident from the increase in DNA fragmentation and numbers of apoptotic cells. Mechanisms of toxicity and cell damage in the beta cell lines, 1.lB4 and MIN6, were consistent with previously established results using rodent cell models and isolated islets. This is the first study to report cellular responses of 1.1B4, GLUTag and Alpha TCI clone 9 cells under diabetic conditions The results indicate that 1.1 B4 cells represent a good model of human islet beta cells for studying beta cell biology. Further, whereas MIN6 and GLUTag cells are sensitive to cytotoxic damage, Alpha Tel clone 9 cells exhibit resistance due to their relatively higher expression of catalase and lower expression of Glut2. Further dissection of molecular pathways could aid in better understanding of mechanisms involved in diabetes, leading to new therapeutic approaches.
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Wong, Ching-hang. "Cell-cell interactions and cell junction dynamics in the mammalian testis." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31993084.
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Turhan, Ali G. "Clonality of normal and malignant hemopoiesis." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/31369.
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In the normal adult human, hemopoiesis appears to be maintained by the simultaneous activity of many stem cell-derived clones. Conversely, most examples of human myeloid malignancies have been shown to represent clonal populations arising as a result of the unregulated expansion of a single transformed hemopoietic stem cell. The limits of the proliferative capacity of normal hemopoietic stem cells in humans and their persistence in hemopoietic malignancies have, however, not been extensively Investigated. One of the most likely reasons for this is the lack, until very recently, of a widely applicable method to analyze the clonality status of human cell populations. Methylation analysis of two polymorphic genes. HPRT and PGK, now allows such studies to be performed in approximately 50 % of females.
The possibility that normal human hemopoietic stem cells might have the capacity to mimic the behaviour of some transformed stem cells by generating clones of progeny that could dominate the entire hemopoietic system was then examined. Such a phenomenon has been well documented in animal models of marrow cell transplantation. I therefore undertook an analysis of all allogeneic marrow transplants performed over a 1 to 1-1/2 year period where the genotype of the donor made clonality analysis using the HPRT or PGK systems possible. Using this approach, I obtained evidence in two patients suggesting that a single or, at most, a very small number of normal primitive hemopoietic stem cells were able to reconstitute the hemopoietic system. In one case the data suggested that such reconstitution was likely to have derived from a stem cell with both lymphopoietic and myelopoietic potential. However, in all other cases hemopoiesis in the transplant recipient was found to be polyclonal. Such findings indicate that clonal dominance in the hemopoietic system is not sufficient to infer that a genetically determined neoplastic change has occurred. In addition, these findings have implications for the design of future gene therapy protocols.
The same methodology was also applied to investigate the clonality of different hemopoietic cell populations in patients with chronic myelogenous leukemia (CML) and essential thrombocytosis (ET). In both of these myeloproliferative disorders, the neoplastic clone produces terminally differentiated progeny that appear minimally different from normal. Data from the CML studies confirmed the non-clonal nature of the cells emerging in long-term CML marrow cultures. Similarly, patients transplanted with cultured autologous marrow were shown to undergo polyclonal and bcr-negative reconstitution of their hemopoietic system. Analysis of a series of patients with a clinical diagnosis of ET showed that polyclonal hemopoiesis in the presence of an amplified neoplastic clone is not a rare event in this disorder, and that clonality results do not always correlate with other neoplastic markers associated with myeloproliferative diseases in general. Another example of polyclonal hemopoiesis in the presence of an amplified neoplastic clone was demonstrated in a patient with Ph¹-positive ALL whose disease appeared to have originated in a lymphoid-restricted stem cell.
The studies described in this thesis reveal a level of complexity of normal and neoplastic stem cell dynamics not previously documented. They highlight the need for more precise information about the molecular basis of regulatory mechanisms that govern hemopoietic cell proliferation and survival at every level of differentiation. Finally they support the accumulating evidence that acquisition of full malignant potential requires several additive genetic changes first postulated many years ago as the somatic mutation theory of carcinogenesis.Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate
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Gronthos, Stan. "Stromal precursor cells : purification and the development of bone tissue." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phg8757.pdf.
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Bibliography: leaves 152-223. Experiments were designed to identify and purify human bone marrow stromal precursor cells by positive immunoselection, based on the cell surface expression of the VCAM-1 and STRO-1 antigens. The data presented demonstrates a hierarchy of bone cell development in vitro.
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O'Malley, James. "Novel cell surface markers identify routes to iPS cells." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/8883.
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The generation of induced pluripotent stem cells (iPSCs) presents a challenge to normal developmental processes. The low efficiency and heterogeneity of most methods have hindered understanding of the precise molecular mechanisms promoting, and roadblocks preventing, efficient reprogramming. While several intermediate populations have been described, it has proved difficult to characterize the rare, asynchronous transition from these intermediate stages to iPSCs. The rapid expansion of a minor population of reprogrammed cells can also obscure investigation of relevant processes. Understanding of the biological mechanisms essential for successful iPSC generation requires both accurate capture of cells undergoing the reprogramming process and identification of the associated global gene expression changes. Here we demonstrate that reprogramming follows an orderly sequence of stage transitions marked by changes in cell surface markers CD44 and ICAM1, and a Nanog-GFP reporter. RNA-sequencing (RNA-seq) analysis of these populations demonstrates two waves of pluripotency gene up-regulation, and unexpectedly, transient up-regulation of multiple epidermis-related genes, demonstrating that reprogramming is not simply the reversal of normal developmental processes. This novel high-resolution analysis enables the construction of a detailed reprogramming route map, and this improved understanding of the reprogramming process will lead to novel reprogramming strategies.