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Stem Cell Res Ther. 2016 Aug 11;7(1):108. doi: 10.1186/s13287-016-0374-4.

Exendin-4 enhances the differentiation of Wharton's jelly mesenchymal stem cells into insulin-producing cells through activation of various β-cell markers.

Author information

1
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
2
Gynecology and Obstetrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
3
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. hala.elmesallamy@hotmail.com.

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.

KEYWORDS:

Diabetes mellitus; Exendin-4; Insulin-producing cells; Mesenchymal stem cells; Wharton’s jelly

PMID:
27515427
PMCID:
PMC4981957
DOI:
10.1186/s13287-016-0374-4
[Indexed for MEDLINE]
Free PMC Article

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