Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/27819
Title: Cellular therapy of Diabetes Mellitus
Authors: CHEN KIN FOONG
Keywords: cellular gene therapy diabetes hepatocytes bone marrow mesenchymal stromal cells
Issue Date: 13-Mar-2009
Source: CHEN KIN FOONG (2009-03-13). Cellular therapy of Diabetes Mellitus. ScholarBank@NUS Repository.
Abstract: Current gene- and cell-based therapies have significant limitations which impede clinical application. Taking diabetes mellitus as a paradigm, we show that ex vivo electrotransfer of glucose-responsive promoters-regulated nonviral insulin expression vectors in primary adult somatic cells i.e. murine and porcine hepatocytes and porcine bone marrow mesenchymal stem cells (PBMMSCs). Quasi-physiological glucose-regulated transgenic proinsulin transcription and insulin secretion was achieved in vitro. In two separate in vivo studies, immediate intrahepatic implantation of plasmid-electroporated syngeneic and autologous primary hepatocytes durably corrected murine and porcine streptozotocin (STZ)-induced diabetes, respectively. Importantly, fasting hypoglycaemia did not occur. Early correction of porcine diabetes ameliorated diabetes-associated metabolic derangements, tissue-level transcriptome changes and structural complications. In another in vivo experiment, xenotransplantation of modified PBMMSCs in NOD-scid mice ameliorated STZ-diabetes. In conclusion, this simple strategy is safe and effective, and may have more general application for the treatment of other diseases caused by specific protein deficiencies.
URI: http://scholarbank.nus.edu.sg/handle/10635/27819
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