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Title: Transplantation and improvement of mouse embryo progenitor-derived insulin-producing cells for type 1 diabetes therapy
Keywords: Type 1 diabetes, encapsulation, transplantation, insulin-producing cells
Issue Date: 30-Jul-2010
Citation: SHAO SHIYING (2010-07-30). Transplantation and improvement of mouse embryo progenitor-derived insulin-producing cells for type 1 diabetes therapy. ScholarBank@NUS Repository.
Abstract: The application of islet transplantation to cure type 1 diabetics is impeded by shortage of cadaveric pancreata and requirement of life-long immunosuppression. In this thesis study, expandable insulin-producing MEPI-1 cells derived from mouse embryonic progenitor were immuno-isolated by microencapsulation. After peritoneal transplantation of encapsulated MEPI-1 cells in streptozotocin-induced diabetic mice, normoglycemia or moderate hypoglycemia was achieved for 2.5 months before a relapse of hyperglycemia. Importantly, a second transplantation in relapsed mice was as effective in correcting hyperglycemia as in the first one. The relapse could be due to necrosis resulting from a slow increase of cell mass by proliferation. To improve MEPI-1 cell maturation toward mature primary ß-cells, the level of MafA, a key transcription factor for promoting ß-cell maturation but expressed low in MEPI-1 cells, was restored by infection of lentivirus expressing MafA. MafA-restored MEPI-1 cells up-regulated expression of genes for many molecules important for ß-cell function, slowed cell proliferation, enhanced insulin content, lowered basal insulin release but markedly improved glucose-induced insulin secretion. These data demonstrated a promising way for the treatment of type 1 diabetics using embryonic stem cells as the ß-cell source while preventing immunosuppression via immune-isolation of cells.
Appears in Collections:Ph.D Theses (Open)

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