Exendin-4 enhances the differentiation of Wharton's jelly mesenchymal stem cells into insulin-producing cells through activation of various β-cell markers
Kassem, Dina; Kamal, Mohamed; El-Kholy, Abd El Latif G.; El-Mesallamy, Hala O.;
Abstract
Background: Diabetes mellitus is a devastating metabolic disease. Generation of insulin-producing cells (IPCs) from stem cells, especially from Wharton's jelly mesenchymal stem cells (WJ-MSCs), has sparked much interest recently. Exendin-4 has several beneficial effects on MSCs and β cells. However, its effects on generation of IPCs from WJ-MSCs specifically have not been studied adequately. The purpose of this study was therefore to investigate how exendin-4 could affect the differentiation outcome of WJ-MSCs into IPCs, and to investigate the role played by exendin-4 in this differentiation process. Methods: WJ-MSCs were isolated, characterized and then induced to differentiate into IPCs using two differentiation protocols: protocol A, without exendin-4; and protocol B, with exendin-4. Differentiated IPCs were assessed by the expression of various β-cell-related markers using quantitative RT-PCR, and functionally by measuring glucose-stimulated insulin secretion. Results: The differentiation protocol B incorporating exendin-4 significantly boosted the expression levels of β-cell-related genes Pdx-1, Nkx2.2, Isl-1 and MafA. Moreover, IPCs generated by protocol B showed much better response to variable glucose concentrations as compared with those derived from protocol A, which totally lacked such response. Furthermore, exendin-4 alone induced early differentiation markers such as Pdx-1 and Nkx2.2 but not Isl-1, besides inducing late markers such as MafA. In addition, exendin-4 showed a synergistic effect with nicotinamide and β-mercaptoethanol in the induction of these markers. Conclusions: Exendin-4 profoundly improves the differentiation outcome of WJ-MSCs into IPCs, possibly through the ability to induce the expression of β-cell markers.
Other data
Title | Exendin-4 enhances the differentiation of Wharton's jelly mesenchymal stem cells into insulin-producing cells through activation of various β-cell markers | Authors | Kassem, Dina ; Kamal, Mohamed ; El-Kholy, Abd El Latif G.; El-Mesallamy, Hala O. | Keywords | Diabetes mellitus;Exendin-4;Insulin-producing cells;Mesenchymal stem cells;Wharton's jelly | Issue Date | 1-Jan-2016 | Publisher | BMC | Journal | Stem Cell Research and Therapy | ISSN | 1757-6512 | DOI | 10.1186/s13287-016-0374-4 | PubMed ID | 27515427 | Scopus ID | 2-s2.0-84992028877 | Web of science ID | WOS:000384590200002 |
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