Abstract

The use of different sources of stem cells including embryonic and mesenchymal stem cells is a novel therapy for diabetic’s patients. However the efficiency of differentiation is not enough to complete treatment. An important point in the induction of stem cells into IPCs in vitro is the role of the pancreatic niche (which includes the stromal and epithelial niche). It can physically contact to adjacent cells and influence stem cell behavior via close range signaling. In this respect, we hypnotized that Pancreatic Stromal Cell (PSC) as a fundamental factor of the stromal niche may have an effective role in the generation IPCs (i.e, the efficiency of differentiation and function of newlyformed β-cells) in vitro. Therefore in this study, MSCs derived from umbilical cord (UC-MSCs) vain and bone marrow (BM-MSCs) was selected to differentiate into IPCs in co-culture with rat PSCs. Our results have demonstrated that only BM-MSCs were able to differentiate into IPCs. Cells in Islet-like clusters with (out) co-cultured with rat pancreatic stromal cells, produced insulin and C-peptide and released them to culture medium at the end of the induction protocol; however they did not respond to glucose challenges very well. The presence of rat pancreatic stromal cells, up-regulated the expressions of insulin, Glut2, and Nkx2.2 were at the mRNA level in IPCs. These results suggested that rat PSCs possibly affect MSCs differentiation into IPCs by increasing the number of immature β-cells.

Highlights

  • Type I diabetes mellitus is a chronic disease resulting from the selective autoimmune destruction of pancreatic insulin-producing β-cells [1]

  • The mesenchymal stem cells were successfully isolated from human umbilical cord vein which named UC-Mesenchymal Stem Cells (MSCs)

  • The data revealed that unlike bone marrow derived MSCs (BM-MSCs), UC vein MSCs (UC-MSCs) could not differentiate into adipocytes (Figure 2B) when stained by oil red dye

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Summary

Introduction

Type I diabetes mellitus is a chronic disease resulting from the selective autoimmune destruction of pancreatic insulin-producing β-cells [1]. Over the past two decades, transplantation of pancreatic islet cells as a potential cure for type I diabetes mellitus has become the subject of intense interest [3,4], the problem of the worldwide shortage of transplant-ready islets has yet to be resolved. It has recently been reported that bone marrow derived MSCs (BM-MSCs) can be induced into Insulin-Producing Cells (IPCs) [9]. The source of bone marrow (BM) is limited and the amount of BM-MSCs and their differentiation capacity decrease with age [10]. The potential of UC vein MSCs (UC-MSCs) have not been investigated

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