PDX-1 mRNA-induced reprogramming of mouse pancreas-derived mesenchymal stem cells into insulin-producing cells in vitro

Clin Exp Med. 2015 Nov;15(4):501-9. doi: 10.1007/s10238-014-0319-0. Epub 2014 Oct 28.

Abstract

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.

Keywords: Insulin-producing cells (IPCs); PDX-1 mRNA; Pancreas-derived mesenchymal stem cells (pMSCs); Reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cells, Cultured
  • Homeodomain Proteins / genetics*
  • Insulin / metabolism*
  • Insulin Secretion
  • Male
  • Mesenchymal Stem Cells / physiology*
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism*
  • Trans-Activators / genetics*
  • Transfection

Substances

  • Homeodomain Proteins
  • Insulin
  • RNA, Messenger
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein