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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 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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Treatment of spinal cord injury by transplantation different types of stem cells
Dubišová, Jana ; Kubinová, Šárka (advisor) ; Cizkova, Dasa (referee)
Spinal cord injury (SCI) is complicated injury with serious socioeconomic consequences for the patient and his whole family. Big difficulty cause also extremely high living expenses for the patient with this type of injury. That's why there is a need for therapeutic methods which would help patients after SCI to recover the lost functions and be able at least partially to return to their normal life. Different therapeutic methods are being used for SCI treatment. In this study we used four various types of stem cells: human bone marrow stem cells (hBM-MSCs), human umbilical cord mesenchymal stem cells (hUC-MSCs), neural precursors derived from induced pluripotent stem cells (iPS-NPs) and neural stem cell line derived from human fetal spinal cord tissue (SPC-01). These cells have been transplanted intrathecally or intraspinally 7 days after induction of the experimental model of SCI in the rat. We studied expressions of genes related to neurogenesis, growth factors and inflammation 10 and 28 days after SCI. Our analysis showed significant changes in gene expression 10 days after SCI. Significant up-regulation in expression of vascular endothelial growth factor (Vegf), ciliary neurotrophic factor (Cntf) and interferon regulatory factor 5 (Irf5) were found after transplantation of hBM-MSCs and hUC-...
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