Role of Bone Marrow-Derived Mesenchymal Stem Cells Differentiate into β Cells in the Pancreatic Microenvironment
Chun-Yan Deng
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen 518020, China.
Ya-Li Yang
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen 518020, China.
Feng Gao
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen 518020, China.
Hui Qi
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen 518020, China.
Fu-Rong Li *
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen 518020, China.
*Author to whom correspondence should be addressed.
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.
Keywords: Mesenchymal stem cells, transplantation, differentiation, pancreatic microenvironment, insulin-producing cells