Effect of GLP1 and Exendin-4 on the Differentiation of Periosterum-derived Progenitor Cells into Insulin Producing Cells

초록

A type 1 diabetes mellitus (T1DM) is characterized by T cell-mediated autoimmune destruction of pancreatic cells. For the treatment of the disease, patients require either replacement or regeneration of insulin-producing cells (IPCs). However the treatment has limited clinical relevance due to the shortage of pancreas donors. We expect that mesenchymal stem cells (MSCs) are clinically applicable to promote glucose homeostasis, because they have the potential of autologous, self-renewing, and sufficient growth rates. Periosteum-derived progenitor cells (PDPCs) are known to be a kind of MSCs. It is easy to isolate PDPCs and they have higher growth potency than the other tissue-derived MSCs. In this study, we investigated in vitro differentiation of PDPCs into IPCs for cell therapy. PDPCs have CD9/CD90/CD166 as positive surface markers and CD45 as a negative surface marker. For the differentiation into IPCs, PDPCs were cultured in serum-free DMEM/F12 with various supplements. Especially PDX1 plays a distinct role in the proliferation of differentiating cells. Expression of PDX1 is necessary for the initial differentiation and growth of precursors within the developing IPCs. This study suggests the action of glucagon-like peptide 1 (GLP1) and exendin-4 in enhancing the growth of IPCs, and it may rely on the activation of PDX1 in IPCs. Effect of GLP1 and exendin-4 for the differentiation of PDPCs into IPCs was confirmed by using immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) analysis demonstrated the quantity of insulin produced by the differentiated cells. By using real-time quantitative polymerase chain reaction (RT-qPCR), expression levels of insulin and other pancreatic beta-cell related genes were detected. In conclusion, PDPCs could be used as a superior source of IPCs. Additional animal test is needed for further study. We hope that PDPCs can provide a true cure for T1DM in the near future.