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|Title:||Transplantation and improvement of mouse embryo progenitor-derived insulin-producing cells for type 1 diabetes therapy||Authors:||SHAO SHIYING||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.||URI:||http://scholarbank.nus.edu.sg/handle/10635/20701|
|Appears in Collections:||Ph.D Theses (Open)|
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