PDX-1 mRNA-induced reprogramming of mouse pancreas-derived mesenchymal stem cells into insulin-producing cells in vitro
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Pancreatic islet transplantation has remained an effective therapy for type 1 diabetes since 2000. Its widespread use has been prohibited by the shortage of suitable donors. It is critical to explore an applicable alternative for β-cell replacement. This study was performed to generate insulin-producing cells (IPCs) from pancreas-derived mesenchymal stem cells (pMSCs). pMSCs were isolated from discarded pancreatic tissue in the filter liquor during islet isolation procedure in mice and ex vivo expanded in culture. IPCs were induced by transfection of pancreas and duodenal transcription factor 1 (PDX-1) mRNA in vitro. Some islet characteristics were identified on pMSC-derived IPCs in mRNA and protein levels. Our results demonstrated that mouse pMSCs can be transdifferentiated into effective glucose-responsive insulin-producing cells through transfecting synthetic modified PDX-1 mRNA in vitro. The study of PDX-1 mRNA-induced pMSC reprogramming may pave the way toward the development of a novel β-cell source for the treatment of diabetes.
KeywordsPancreas-derived mesenchymal stem cells (pMSCs) Reprogramming PDX-1 mRNA Insulin-producing cells (IPCs)
This study was financially supported by the Major Science and Technology Projects of China (No. 2013ZX10001-004-002-005), National Natural Science Foundation of China (No. 21075097), the National Natural Science Foundation of China (81070614), National Natural Science Foundation of Hubei province (2012FFA037), Natural Science Support Foundation for graduated students of Hubei University of Medicine (2011QDZR-8) and Foundation of Hubei Educational Committee(B20122411). Authors are grateful to Dr. Long-Jun Dai of University of British Columbia in Canada for his critical review and discussion of the manuscript.
Conflict of interest
All animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards.
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