ENDOTHELIAL- EPITHELIAL INTERACTIONS Blood vessels friends or foes?

University dissertation from Stem Cell Center, Dept of Laboratory Medicine, Lund

Abstract: Diabetes affects enormous amounts of patients. In type 1 diabetes the insulin producing β cells in the islet of Langerhans are destroyed by the immune system. The β cells, which are located in the pancreas, regulate blood glucose levels. The lack of insulin production requires administration of insulin. This is accomplished by insulin injections. Even though the treatment methods have been improved, we are still not able to artificially regulate the blood glucose levels as evenly as the β cells. The fluctuations of the blood glucose levels results in the long term in a number of complication, among the diabetic retinopathy. Diabetic retinopathy is the leading cause of blindness among the younger population. Both to reduce the complications of diabetes and to find cures of the disease is important. By using a model for diabetic retinopathy in mice we have been able to show that lack of the molecule N-CAM is protecting against the pathological neovascularization affecting diabetic patients. The last 10 years have proven it possible to cure diabetes through transplantations of islets of Langerhans from cadaveric donors. The transplantations requires suppression of the immune response, this could lead to other complications. The amount of diabetic patients in need of transplantations far exceeds the availability of donors. The use of stem cells to produce insulin producing β cells might be a possible way. To be able to direct the stem cells into β cells it is important to understand how these cells form during embryo development. By the use of mice we have been able to study how blood vessels regulate the growth of the precursors of β cells. We have also been able to show that the formation of a tubular system in the pancreas is important for the regulation of which cell types that are to be formed. Our results can be used to develop better methods for the production of β cells from stem cells.

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