Background: Diabetes mellitus is a devastating metabolic disease. Generation of insulin-producing cells (IPCs) from\nstem cells, especially from Whartonâ��s jelly mesenchymal stem cells (WJ-MSCs), has sparked much interest recently.\nExendin-4 has several beneficial effects on MSCs and �² cells. However, its effects on generation of IPCs from WJ-MSCs\nspecifically have not been studied adequately. The purpose of this study was therefore to investigate how exendin-4\ncould affect the differentiation outcome of WJ-MSCs into IPCs, and to investigate the role played by exendin-4 in this\ndifferentiation process.\nMethods: WJ-MSCs were isolated, characterized and then induced to differentiate into IPCs using two differentiation\nprotocols: protocol A, without exendin-4; and protocol B, with exendin-4. Differentiated IPCs were assessed by\nthe expression of various �²-cell-related markers using quantitative RT-PCR, and functionally by measuring glucosestimulated\ninsulin secretion.\nResults: The differentiation protocol B incorporating exendin-4 significantly boosted the expression levels of\n�²-cell-related genes Pdx-1, Nkx2.2, Isl-1 and MafA. Moreover, IPCs generated by protocol B showed much better\nresponse to variable glucose concentrations as compared with those derived from protocol A, which totally\nlacked such response. Furthermore, exendin-4 alone induced early differentiation markers such as Pdx-1 and\nNkx2.2 but not Isl-1, besides inducing late markers such as MafA. In addition, exendin-4 showed a synergistic\neffect with nicotinamide and �²-mercaptoethanol in the induction of these markers.\nConclusions: Exendin-4 profoundly improves the differentiation outcome of WJ-MSCs into IPCs, possibly through the\nability to induce the expression of �²-cell markers.
Loading....