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Mesenchymal stem cells and the possibility of their transdifferentiation into insulin producing cells.
Dostálová, Veronika ; Holáň, Vladimír (advisor) ; Čečrdlová, Eva (referee)
Mesenchymal stem cells (MSCs) have been demonstrated in almost all tissues of the body. Their main source is bone marrow and adipose tissue. These cells are multipotent, e.g. they are capable of differentiating into a variety of cell types. They are able to migrate into damaged tissues. Their other relevant property is a specific suppression of imunity. In the body they serve as precursors for specialized cell types and they also participate in formation of specific tissue microenvironment. Their properties represent a great potential in a wide range of clinical therapies. Besides other possible applications they could be used in the therapy of diabetes mellitus type one. During this disease insulin producing -cells are destroyed. MSCs have been used in experimental in vitro and in vivo studies to differentiate into insulin producing cells. However these cells are not able to produce sufficient amounts of insulin to exclude the supportive administration of exogenous insulin. Therefore there is a need for further research in this field of possible therapy.
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Differentiation of pancreatic stem cells into insulin producing β-cells.
Leontovyč, Ivan ; Saudek, František (advisor) ; Štechová, Kateřina (referee) ; Holáň, Vladimír (referee)
Diabetes mellitus (DM) is a severe and frequent disease with increasing prevalence. It is not possible to achieve long term cure without late complications. Recent advances in cell fate modifications open a pathway to alternative cell therapies for DM cure. My doctoral thesis "Differentiation of pancreatic stem cells into insulin producing β- cells" is focused on the development of a new source of insulin secreting cells for transplantation. Combinatorial testing of numerous potential transcription factors and epigenetic modifiers resulted in a final protocol for the reprogramming pancreatic of exocrine cells into insulin secreting cells. The key transcriptional factors TF (Pdx1, Ngn3 a MafA) were applied in the form of synthetic mRNA. In four independent experiments we applied transcriptional factors in a specific sequence, thus obtaining 14.3 ± 1.9 % insulin positive cells. When challenged in vitro by the glucose levels of 2.5 and 20 mmol/l glucose, respectively, these cells exhibited glucose-sensitivity of insulin secretion (842 ± 72 and 1 157 ± 58 pg insulin/µg DNA/ml, n=5). They also demonstrated a sensitivity of insulin secretion (863 ± 78 and 1 025 ± 66 pg insulin/µg DNA/ml, n=5) to the concentration of depolarization agent KCl applied at 0 and 30 mmol/l, respectively together with 2.5...
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Mesenchymal stem cells and the possibility of their transdifferentiation into insulin producing cells.
Dostálová, Veronika ; Holáň, Vladimír (advisor) ; Čečrdlová, Eva (referee)
Mesenchymal stem cells (MSCs) have been demonstrated in almost all tissues of the body. Their main source is bone marrow and adipose tissue. These cells are multipotent, e.g. they are capable of differentiating into a variety of cell types. They are able to migrate into damaged tissues. Their other relevant property is a specific suppression of imunity. In the body they serve as precursors for specialized cell types and they also participate in formation of specific tissue microenvironment. Their properties represent a great potential in a wide range of clinical therapies. Besides other possible applications they could be used in the therapy of diabetes mellitus type one. During this disease insulin producing -cells are destroyed. MSCs have been used in experimental in vitro and in vivo studies to differentiate into insulin producing cells. However these cells are not able to produce sufficient amounts of insulin to exclude the supportive administration of exogenous insulin. Therefore there is a need for further research in this field of possible therapy.
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