The Effects of Exendine-4 on Insulin Producing Cell Differentiation from Rat Bone Marrow-Derived Mesenchymal Stem Cells

Document Type : Original Article

Authors

1 Cell and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Cell and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;Department of Anatomical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Objective
The aim of this study was to evaluate the effect of exendin-4 (EX-4) on differentiation of insulin-producing cells (IPCs) from rat bone marrow-derived mesenchymal stem cells (RAT-BM-MSCs).
Materials and Methods
In this experimental study, RAT-BM-MSCs were cultured and the cells characterized by flow cytometry analysis of cell surface markers. RAT-BM-MSCs were subsequently treated with induction media with or without EX-4. After induction, the presence of IPCs was demonstrated with dithizone (DTZ) staining and gene expression profiles for pancreatic cell differentiation markers (PDX-1, GLUT-2, insulin) were assessed using reverse transcription polymerase chain reaction (RT-PCR). Insulin excreted from differentiated cells was analyzed with radioimmunoassay (RIA). The two-tailed student’s t-test was used for comparison of the obtained values.
Results
The percentage of DTZ-positive cells significantly increased in EX-4 treated cells (p < 0.05). Expression of the islet-associated genes PDX-1, GLUT-2 and insulin genes in EX-4 treated cells was markedly higher than in the cells exposed to differentiation media without EX-4. RIA analysis demonstrated significant release of insulin with the glucose challenge test in EX-4 treated cells compared to EX-4 untreated cells.
Conclusion
The results of this study have demonstrated that EX-4 can enhance differentiation of IPCs from RAT-BM-MSCs.

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