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Studies on Coexpression of PDX1 and Betacellulin in Bone Marrow Mesenchymal Stem Cells Differentiating into Insulin-secreting Cells
Jin-Xing Jiang1, Li-Sha Li1, Hong-Bin Xie1, Shu-Yan Zhou1, Xiao-Dan Zhang1, Fu-Rong Li1,2, Hui Qi1*
1Clinical Medical Research Center, Second Clinical Medical College Shenzhen People’s Hospital, Jinan University, Shenzhen 518020, China; 2Shenzhen Institute of Gerontology, Shenzhen 518020, China
Abstract: Replacement of β cells by islet transplantation is a novel therapy for diabetes. Mesenchymal stem cells have been proved to be multipotent. This study evaluate the differentiating ability of rat MSCs into insulin- secreting cells by co-expression of PDX1 and BTC. PDX1 is a transcription factor involved in the early endocrine development. Betacellulin (BTC) is a growth factor involved in beta-cell maturation. Co-expression of PDX1 and BTC significantly increased the number of nestin-positive epithelium-like progenitors and islet-like spheroids which differentiated from BMMSCs， and the levels of Insulin and Glut-2 mRNA were elevated significantly. In response to glucose， Pdx1+BTC+MSCs released insulin and C-peptide， but low compared with normal islets. It is concluded that genetic manipulation of Pdx1 and BTC by Tet-on system in combination with appropriate differentiating culture could induce BMMSCs into the pancreatic lineage in vitro and produce islet-like spheroids that could secrete increased levels of insulin in response to glucose. However， compared with the natural pancreas islet， insulin and C peptide secretion was still insufficient.
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