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Induction of testicular stem cell differentiation in mammals.
Strnadová, Karolína ; Tlapáková, Tereza (advisor) ; Krulová, Magdaléna (referee)
Stem cells represent a unique cell source with potential usage in regenerative medicine and organ transplantation. As is known, spermatogonial stem cells are unipotent giving rise to a single cell type, which is sperm. Pluripotency was achieved by isolation and cultivation of these testicular stem cells in a number of researches. Testicular pluripotent stem cells differentiated in conditions in vitro to derivatives of all three germ layers identically as embryonic stem cells. The aim of this thesis is to characterize stem cells and summarize the findings of testicular stem cell research. The main focus of this thesis is on studies of cultivated pluripotent stem cells derived from mouse and human testes and their ability to differentiate under determinate conditions into the cells of ectoderm, mesoderm and endoderm.
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Molecular mechanisms of sterile inflammation in damaged hematopoietic tissue
Čiháková, Zuzana ; Faltusová, Kateřina (advisor) ; Bačová, Barbora (referee)
Hematopoietic tissue is home to hematopoietic stem cells (HSCs), which continuously generate all blood and immune cells. Tissue damage or cellular stress can lead to sterile inflammation. In response to the sterile inflammation, HSCs are activated to proliferate and switch to emergency hematopoiesis. Long-term exposure of hematopoietic tissue to inflammatory signals leads to increased differentiation at the expense of self-renewal of HSCs, DNA damage, and genetic instability, which can lead to cell death, permanent bone marrow damage and hematopoietic damage.
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Morphological variability of the incisor in mutant mice
Lochovská, Kateřina ; Hovořáková, Mária (advisor) ; Churavá, Svatava (referee)
Myš je nejfrekventovaněji používaným experimentálním modelovým organismem pro studium vývoje zubů. Myší funkční dentice obsahuje jeden řezák oddělený od tří molárů dlouhou bezzubou diastemou v každém čelistním kvadrantu. Cílem této práce bylo shrnout poznatky o myší dentici a jejím vývoji se zaměřením na myší řezáky a jejich patologie. Myší řezák je díky svým vlastnostem jedinečným zubem. Charakteristickou vlastností hlodavců jsou právě kontinuálně rostoucí řezáky. Tyto řezáky jsou pokryté sklovinou pouze na labiální straně. Lingvální povrch je tvořen pouze dentinem. Toto je spojeno s asymetrickou abrazí. Nicméně je také častým cílem mutací, ať už v podobě delece nebo jiné modifikace genů. Tyto mutace dentálních signálních drah jsou studovány na mutantních myších jako jsou například Tabby myši, Sprouty nebo Small eye (Sey) mutantní myši a mnoho dalších. Některé mutace jsou homologní k lidským onemocněním. Například X-vázaný tabby (Ta) syndrom u myší je považován za homolog hypohidrotické ektodermální dysplásie (HED) u lidí. Tato mutace napadá velikost řezáku, jeho tvar a pozici stejně jako cytodiferenciaci. Dále se může objevit hypodoncie, anodoncie nebo nějaké morfologické změny napadající ostatní existující zuby. Abnormality v počtu, velikosti a tvaru zubu byly dobře zdokumentovány v lidské...
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Immune response in mammalian species against progenitor cell types including induced pluripotent stem cells (iPSCs)
Kovandová, Barbora ; Drbal, Karel (advisor) ; Krulová, Magdaléna (referee)
Stem cells may be very useful tool for regenerative medicine. They are able to repair any tissue in a human body and cure any damage caused by injury, sickness or aging. But at first, we have to deal with problems, which are connected with their usage - especially their immunogenicity. This bachelor thesis is focused on immunogenicity of embryonal (ESC), induced pluripotent (iPSC) and adult stem cells (ASC). Tissues derived from ESC are in vivo described as strongly immunogenic, although they seem to be immunosuppressive in vitro. Another danger of their usage is their tumorigenic potential. There also exist ethical issues connected with their usage. iPSC were supposed to be a good replacement for ESC, because no immunological nor ethical problems were expected. Surprisingly, they were described as immunogenic, too, even in autologous environment. These cells were also described as tumorigenic; this is the main reason for now why they cannot be used for the replacement therapy. Immunogenicity, so as tumorigenicity of iPSC may be a consequence of their dedifferentiation from somatic back to stem cells. ASC are the only stem cells, which are already used for the replacement therapy (transplantation of bone marrow). Some of them are described as immunosuppressive or tumor-suppressive, other are...
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Immunogenicity of induced pluripotent stem cells (iPSC)
Tejklová, Tereza ; Drbal, Karel (advisor) ; Hájková, Michaela (referee)
Ectopic expression of several transcription factors into the somatic cells allows us to artificially dedifferentiate them into induced pluripotent stem cells (iPSC), which show great promise in regenerative medicine and personalized disease modelling, as well as diagnostic tools. Unique attribute of iPSC is the possibility of creating autologous cells for each patient, which could be used for transplantation without fear of immune rejection. However, cells differentiated from iPSC generally display decreased expression of MHC I glycoproteins, which leads to the activation of NK cells of innate immunity. T cells, the part of adaptive immunity, are activated after recognition of antigen peptide or foreign MHC I glycoproteins only in co-operation with costimulatory molecules, which are not usually expressed on iPSC. During dedifferentiation, cells keep the epigenetic profile of the source cell, which can result in the abnormal expression of genes within derived cell lines. Overall immunogenicity depends on the method of iPSC preparation, with respect to genomic stability. Another important factor is the immune environment of transplantation site as well as the tissue damage caused during transplantation. This results in the presentation of danger signals (DAMPs), which are then recognized by pattern...
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Differentiation of adult stem cells into insulin-producing beta cells
Koblas, Tomáš
Ph.D. Thesis abstract: Diabetes mellitus is a chronic disease characterized by a metabolic disorder in which there is a low level or complete lack of the insulin. Diabetes mellitus type 1 (DM1) is caused by an autoimmune reaction leading to the destruction of the insulin producing beta cells in the pancreas. In consequence, low or non-existent insulin production leads to a complete dependence on exogenous insulin supplementation. DM1 causes serious long-term complications. Although strict control of blood sugar could prevent the onset and development of diabetic complications only 5% of diabetic patients are able to achieve such control. Hence it is evident that the current methods of treatment are neither sufficient to treat this disease, nor prevent late complications in most patients. The most promising therapeutic approach in the treatment of diabetes is the restoring of insulin production. One such method is the transplantation of insulin-producing tissue. However, a lack of available insulin- producing tissue limits such therapeutic approach. Therefore an alternative source of insulin producing cells have to be found to obtain a sufficient amount of safe and efficient insulin producing tissue. Pancreatic stem/progenitor cells could represent such an available alternative source. Despite the evidence...
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Immunogenicity of induced pluripotent stem cells (iPSC)
Tejklová, Tereza ; Drbal, Karel (advisor) ; Hájková, Michaela (referee)
Ectopic expression of several transcription factors into the somatic cells allows us to artificially dedifferentiate them into induced pluripotent stem cells (iPSC), which show great promise in regenerative medicine and personalized disease modelling, as well as diagnostic tools. Unique attribute of iPSC is the possibility of creating autologous cells for each patient, which could be used for transplantation without fear of immune rejection. However, cells differentiated from iPSC generally display decreased expression of MHC I glycoproteins, which leads to the activation of NK cells of innate immunity. T cells, the part of adaptive immunity, are activated after recognition of antigen peptide or foreign MHC I glycoproteins only in co-operation with costimulatory molecules, which are not usually expressed on iPSC. During dedifferentiation, cells keep the epigenetic profile of the source cell, which can result in the abnormal expression of genes within derived cell lines. Overall immunogenicity depends on the method of iPSC preparation, with respect to genomic stability. Another important factor is the immune environment of transplantation site as well as the tissue damage caused during transplantation. This results in the presentation of danger signals (DAMPs), which are then recognized by pattern...
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Immune response in mammalian species against progenitor cell types including induced pluripotent stem cells (iPSCs)
Kovandová, Barbora ; Drbal, Karel (advisor) ; Krulová, Magdaléna (referee)
Stem cells may be very useful tool for regenerative medicine. They are able to repair any tissue in a human body and cure any damage caused by injury, sickness or aging. But at first, we have to deal with problems, which are connected with their usage - especially their immunogenicity. This bachelor thesis is focused on immunogenicity of embryonal (ESC), induced pluripotent (iPSC) and adult stem cells (ASC). Tissues derived from ESC are in vivo described as strongly immunogenic, although they seem to be immunosuppressive in vitro. Another danger of their usage is their tumorigenic potential. There also exist ethical issues connected with their usage. iPSC were supposed to be a good replacement for ESC, because no immunological nor ethical problems were expected. Surprisingly, they were described as immunogenic, too, even in autologous environment. These cells were also described as tumorigenic; this is the main reason for now why they cannot be used for the replacement therapy. Immunogenicity, so as tumorigenicity of iPSC may be a consequence of their dedifferentiation from somatic back to stem cells. ASC are the only stem cells, which are already used for the replacement therapy (transplantation of bone marrow). Some of them are described as immunosuppressive or tumor-suppressive, other are...
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Early embryonal development and morphogenesis of selected organ systems of the rediae and cercariae of Fascioloides magna.
Pankrác, Jan ; Kašný, Martin (advisor) ; Macůrková, Marie (referee)
Fascioloides magna (giant liver fluke) is a digenetic trematode with two-host life cycle and high veterinary importancy. Typical definitive host is a deer (Cervidae), but many other species from different families can be accidentally infected, for example sheep, goat or cattle. Very important role in the life cycle of F. magna has the first host - fresh water snail of the family Lymnaeidae. Three different life stages of F. magna, two of them with ability of reproduction - sporocysts and rediae develop in the body of snail. The third stage - cercaria is produced by rediae. Cercariae are able to escape from the snail, encyst and become infective for the definitive host. Since the second half of the 19th century many researchers studied the development of particular stages in the first intermediate host, but many characteristics of this process are still not fully understood. This thesis should reveal some of unanswered questions concerning to the reproduction and ontogenetic development of trematodes, which is presented on the examples of three organ systems - muscles, nerves and excretory system of rediae and cercariae of F. magna.
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Induction of testicular stem cell differentiation in mammals.
Strnadová, Karolína ; Tlapáková, Tereza (advisor) ; Krulová, Magdaléna (referee)
Stem cells represent a unique cell source with potential usage in regenerative medicine and organ transplantation. As is known, spermatogonial stem cells are unipotent giving rise to a single cell type, which is sperm. Pluripotency was achieved by isolation and cultivation of these testicular stem cells in a number of researches. Testicular pluripotent stem cells differentiated in conditions in vitro to derivatives of all three germ layers identically as embryonic stem cells. The aim of this thesis is to characterize stem cells and summarize the findings of testicular stem cell research. The main focus of this thesis is on studies of cultivated pluripotent stem cells derived from mouse and human testes and their ability to differentiate under determinate conditions into the cells of ectoderm, mesoderm and endoderm.
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