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

• Main Authors: Fereshteh Nejad-Dehbashi, Elham Shahhosseini Pourshoushtary, Layasadat Khorsandi, Mahmoud Hashemitabar, Mahmoud Orazizadeh, Somaieh Bahramzadeh
• Format: Article
• Language: English
• Published: Royan Institute (ACECR), Tehran 2014-06-01
• Series: Cell Journal
• Subjects: Exendin-4; Mesenchymal Stem Cells; Insulin-producing Cells; PDX-1; GLUT-2
• Online Access: http://celljournal.org/library/upload/article/af_265436763334246445553634352264462753422210-Fereshteh%20Nejad-Dehbashi-1.pdf

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.