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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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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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The role of stem and progenitor cells in regeneration of hematopoietic tissue
Faltusová, Kateřina ; Nečas, Emanuel (advisor) ; Hofer, Michal (referee) ; Filipp, Dominik (referee)
Tissue regeneration is a complex and highly orchestrated process dependent on cells with the potential to restore structures and functions and on controlling factors from the tissue microenvironment. Hematopoietic tissue has a high ability to regenerate, which is attributed to the presence of stem cells, but the regeneration of severely damaged adult tissue is still only partially understood. Hematopoietic tissue provides a unique opportunity to study tissue regeneration due to its well-established steady- state structure and function, easy accessibility, advanced research methods, and well-defined embryonic, fetal, and adult stages of development. Embryonic/fetal liver hematopoiesis and adult hematopoiesis recovering from damage share the needto expand populations of progenitors and stem cells in parallel with increasing production of mature blood cells. We analyzed adult hematopoiesis in mice subjected to a submyeloablative dose (6 Gy) of gamma radiation, in which only a few cells with reconstituting capacity survived. We targeted the period of regeneration characterized by the renewed massive production of mature blood cells and the ongoing expansion of immature hematopoietic cells. Cells from the top of the hematopoietic hierarchy, hematopoietic stem cells, and multipotent progenitors are almost missing...
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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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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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The mechanisms and regulation of lineage commitment in hematopoietic stem cell
Tichý, Marko ; Stopka, Tomáš (advisor) ; Svoboda, Ondřej (referee)
Hematopoietic stem cells (HSCs) are crucial for maintaining balanced homeostasis in the human body. HSCs are pluripotent cells, which are able to give rise to many very different cells. HSCs can be found in fetal liver initially during organismal development where they expand and move to their more definitive location, the bone marrow, shortly before birth in humans and mice. HSCs possess to not only recapitulate themselves (self-renew) or proliferate and expand, but are also the first branching point from which subsequent multipotent progenitors and eventually all blood cell lineages are formed thus establishing specific and restricted terminal differentiation pathways. The irreversible decision to initiate and follow a specific differentiation pathway is designated as lineage commitment. The drivers of lineage commitment, which are a base of this thesis, are intrinsic as well as extrinsic factors acting within the stem cell niche, such as transcription factors, chromatin remodeling factors, and cytokines, which are essential for proliferation, survival, self-renewal and lineage commitment decisions. These regulatory factors, working either independently or in mutual coordination, maintain balanced homeostasis of HSC renewal and their differentiation. The goal of this thesis will be to ascribe the...
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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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