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The effect of synthetic modified mRNAs induced proliferation on pancreatic beta cells
Veľasová, Adriana ; Koblas, Tomáš (advisor) ; Bořek Dohalská, Lucie (referee)
Diabetes mellitus is a chronic disease caused by the loss of pancreatic beta cells due to autoimmune destruction or increased apoptosis. Beta-cell deficiency results in reduced insulin production, which plays an important role in glucose metabolism. The number of beta-cells in the body is one of the main factors that influence the development of this chronic disease. Therefore, it is necessary to find a way by which the number of beta-cells of the organism can be increased and thus the insulin production can be restored in a natural way without any need for the use of insulin infusions. However, the ability of beta-cells to divide decreases with age and is virtually nil in adulthood. The study of the cell cycle, especially the early and late cyclins and cyclin-dependent kinases, which act as cell cycle regulators, thus appears to be a promising way to restore natural insulin-producing tissues. In order to increase the number of beta cells entering the cell cycle, we focused on studying the effect of in vitro transcribed (IVT) mRNAs, encoding cyclins type D and cyclin dependent kinases 4 and 6 on stimulating cell division of isolated beta-cells. We found that transfection IVT mRNAs for type D cyclins in combination with cyclin-dependent kinases 4 and 6 significantly increased the proliferation of beta-cells...
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Characterization of pancreatic beta cells after their in vitro proliferation induced by synthetic modified mRNA
Veľasová, Adriana ; Koblas, Tomáš (advisor) ; Černá, Věra (referee)
The origin and development of type I. and II. diabetes mellitus is directly related to homeostasis of proliferation and apoptosis of pancreatic β-cells. Any imbalance that leads to a decrease in the number of β-cells consequently increases the pro- bability of developing this disease. Patients suffering from diabetes mellitus are de- pendent on partial or complete exogenous insulin replacement, as their pancreas is unable to meet the body's insulin needs. Therefore a need for restoration of normal β-cell mass in diabetic patients leads to the attempts to develop new therapeutic approaches that could expand remaining β-cells of the organism and restore phys- iological insulin production. A major obstacle in this regard is a low sensitivity of terminally differentiated β-cells to mitogenic stimuli that could induce the entry of β-cells into the cell cycle. Activation of β-cell proliferation is associated with the G0/G1/S cell cycle transi- tion, which is under the control of retinoblastoma protein (RB). In order to activate cell cycle entry RB must be phosphorylated. RB phosphorylation is provided by specific cell cycle regulators, particularly cyclin-dependent kinases 4 and 6, which associate with family D cyclins. In accordance with the aim of this Diploma thesis, the effect of these cell cycle...
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The effect of synthetic modified mRNAs induced proliferation on pancreatic beta cells
Veľasová, Adriana ; Koblas, Tomáš (advisor) ; Bořek Dohalská, Lucie (referee)
Diabetes mellitus is a chronic disease caused by the loss of pancreatic beta cells due to autoimmune destruction or increased apoptosis. Beta-cell deficiency results in reduced insulin production, which plays an important role in glucose metabolism. The number of beta-cells in the body is one of the main factors that influence the development of this chronic disease. Therefore, it is necessary to find a way by which the number of beta-cells of the organism can be increased and thus the insulin production can be restored in a natural way without any need for the use of insulin infusions. However, the ability of beta-cells to divide decreases with age and is virtually nil in adulthood. The study of the cell cycle, especially the early and late cyclins and cyclin-dependent kinases, which act as cell cycle regulators, thus appears to be a promising way to restore natural insulin-producing tissues. In order to increase the number of beta cells entering the cell cycle, we focused on studying the effect of in vitro transcribed (IVT) mRNAs, encoding cyclins type D and cyclin dependent kinases 4 and 6 on stimulating cell division of isolated beta-cells. We found that transfection IVT mRNAs for type D cyclins in combination with cyclin-dependent kinases 4 and 6 significantly increased the proliferation of beta-cells...
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