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The use of induced pluripotent stem cells in the treatment of spinal cord injury and ALS.
Gajdoš, Roman ; Jendelová, Pavla (advisor) ; Vargová, Lýdia (referee)
Induced pluripotent stem cells (iPSCs) have become a new phenomenon of regenerative medicine. It is obvious that they share some common characteristics with embryonic stem cells (ESCs) such as stemness potential, self-renewal p., differentiation p. iPSCs retain their epigenetic memory, allowing becoming patient-specific and so it is not necessary to apply immunosuppressants. The use of ESCs is controversial, because their acquisition is associated with embryo destruction. As a cell source for iPSCs derivation we can use any somatic cells, however, fibroblasts are preferably used due to their easy availability. With transcriptional reprogramming cocktail (OCT4, SOX2, KLF4, c- MYC / OCT4, SOX2, NANOG, LIN28) we can obtain required iPSCs line, which is then further differentiated into neural precursors (NPCs). These cells can be grafted into lesion site, where they can facilitate regeneration by several mechanisms (cell replacement, protective effect, facilitation the expression of trophic factors). Nevertheless, here we are still dealing with the risk of tumorogenesis or low cell derivation efficiency that limits the use of iPSCs in clinical practice. In this thesis we will therefore mainly focus on the therapeutic potential of iPSCs in preclinical studies, their use in the treatment of...
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The effect of immunosupression on cell therapy in mouse model of Alzeimer's disease
Gajdoš, Roman ; Jendelová, Pavla (advisor) ; Chmelová, Martina (referee)
Alzheimer's disease is a chronic, progressive, neurodegenerative disease. It belongs to the most common type of dementia and worldwide it is statistically the fifth cause of mortality. The most common morphological markers are insoluble β amyloid plaques, hyperphosforylated tau proteins and formation of neurofibrilar tangles. Among the manifestations of the disease is amyloid angiopathy, synaptic transmission disorders and subsequent apoptosis, deterioration of cognitive functions and brain atrophy. Studies have shown that administration of mesenchymal stem cells (MSC) has an immunomodulatory effects and it can reduce the production and storage of β amyloid and thus improve cognitive functions. In preclinical studies, which are conducted in transgenic mice and often use xenografts, administration of immunosuppresion may lead to variety of positive or negative effects which can affect the results of the experiment. The subject of the master's thesis was to determine the effect of immunosuppression on experimental therapy with MSC in various time windows of AD progression (model 3xTg). At which scale and combination of immunosupression will influence the cell therapy's effects, the length of graft survival, mortality of experimental animals and changes at the cellular level. We have also assessed...
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The effect of immunosupression on cell therapy in mouse model of Alzeimer's disease
Gajdoš, Roman ; Jendelová, Pavla (advisor) ; Chmelová, Martina (referee)
Alzheimer's disease is a chronic, progressive, neurodegenerative disease. It belongs to the most common type of dementia and worldwide it is statistically the fifth cause of mortality. The most common morphological markers are insoluble β amyloid plaques, hyperphosforylated tau proteins and formation of neurofibrilar tangles. Among the manifestations of the disease is amyloid angiopathy, synaptic transmission disorders and subsequent apoptosis, deterioration of cognitive functions and brain atrophy. Studies have shown that administration of mesenchymal stem cells (MSC) has an immunomodulatory effects and it can reduce the production and storage of β amyloid and thus improve cognitive functions. In preclinical studies, which are conducted in transgenic mice and often use xenografts, administration of immunosuppresion may lead to variety of positive or negative effects which can affect the results of the experiment. The subject of the master's thesis was to determine the effect of immunosuppression on experimental therapy with MSC in various time windows of AD progression (model 3xTg). At which scale and combination of immunosupression will influence the cell therapy's effects, the length of graft survival, mortality of experimental animals and changes at the cellular level. We have also assessed...
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|
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The use of induced pluripotent stem cells in the treatment of spinal cord injury and ALS.
Gajdoš, Roman ; Jendelová, Pavla (advisor) ; Vargová, Lýdia (referee)
Induced pluripotent stem cells (iPSCs) have become a new phenomenon of regenerative medicine. It is obvious that they share some common characteristics with embryonic stem cells (ESCs) such as stemness potential, self-renewal p., differentiation p. iPSCs retain their epigenetic memory, allowing becoming patient-specific and so it is not necessary to apply immunosuppressants. The use of ESCs is controversial, because their acquisition is associated with embryo destruction. As a cell source for iPSCs derivation we can use any somatic cells, however, fibroblasts are preferably used due to their easy availability. With transcriptional reprogramming cocktail (OCT4, SOX2, KLF4, c- MYC / OCT4, SOX2, NANOG, LIN28) we can obtain required iPSCs line, which is then further differentiated into neural precursors (NPCs). These cells can be grafted into lesion site, where they can facilitate regeneration by several mechanisms (cell replacement, protective effect, facilitation the expression of trophic factors). Nevertheless, here we are still dealing with the risk of tumorogenesis or low cell derivation efficiency that limits the use of iPSCs in clinical practice. In this thesis we will therefore mainly focus on the therapeutic potential of iPSCs in preclinical studies, their use in the treatment of...
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