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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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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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Immunogenicity of stem cells and their derivatives
Doležalová, Nikola ; Holáň, Vladimír (advisor) ; Kubinová, Šárka (referee)
Immunogenicity of stem cells and their derivatives Nikola Doležalová Abstract Stem cells (SCs) have the potential to be used in regenerative medicine on the basis of their differentiation capacity and promising immunological properties, including low expression of histocompatibility antigens and costimulatory molecules, or secretion of suppressive cytokines. Their immunogenicity has often been ignored in the past but it is becoming clear that rejection of genetically incompatible SCs represents a very common issue. At present, SCs are extensively studied from the immunological point of view, since it represents a critical aspect of the safety of SC therapy. This thesis presents an overview of current knowledge about immunogenicity of SCs and their derivatives, including both pluripotent SCs (embryonic and induced pluripotent SCs) and adult SCs (mesenchymal, limbal, neural, haematopoietic and umbilical cord blood SCs). The expression of immunologically relevant molecules on their surface and interaction with the immune cells in vitro and in vivo will be discussed, together with suggestions for overcoming the immunological barriers for transplantation. Detailed analysis of these aspects necessarily has to precede the safe clinical translation of SC therapies.
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