Role of Bone Marrow-Derived Mesenchymal Stem Cells Differentiate into β Cells in the Pancreatic Microenvironment

Abstract

Aims: Mesenchymal stem cells (MSCs) can differentiate into multiple cell types including insulin-producing cells. However, these cells usually cannot be directed to efficiently differentiate into β cells in vitro. The present study aimed to explore whether the pancreatic microenvironment could induce bone marrow-derived (BM)-MSCs to differentiate into β cells to compensate for insufficient β-cells. Methodology: We directly transplanted male enhanced green fluorescence protein (EGFP)-expressing BM-MSCs into the pancreas of female diabetic Sprague-Dawley rats by multi-point injection. Results: BM-MSCs could restore serum insulin and C-peptide levels and reverse hyperglycemia by intra-pancreatic transplantation. BM-MSCs from male donors could differentiate into pancreatic stem/progenitor cells and β cells under female pancreas micro-environment. Neogenesis islets derived from BM-MSCs were verified in pancreatic tissue by histology and the expression of genes related to β cell gene biomarker was determined by RT-PCR and quantitative real time-PCR. Y-chromosome SRY and PDX-1 mRNA have expressed simultaneously in neogenesis β cells. Polyploidy and aneuploid DNA were not observed. Conclusion: This study showed that transplanted BM-MSCs did not fuse with pancreatic cells and could contribute to repair, paracrine and differentiation into new islet β cells in the pancreatic microenvironment.