MicroRNAs can effectively induce formation of insulin-producing cells from mesenchymal stem cells

J Tissue Eng Regen Med. 2017 Dec;11(12):3457-3468. doi: 10.1002/term.2259. Epub 2017 Apr 10.

Abstract

MicroRNAs regulate insulin secretion, pancreatic development and beta cell differentiation. However, the function of microRNAs in the formation of insulin-producing cells (IPCs) from adult stem cells is poorly understood. We examine the microRNA expression profile in nestin-positive umbilical cord-derived mesenchymal stem cells (N-UCMSCs) and nestin-positive pancreatic mesenchymal stem cells using a deep sequencing approach. We also selected specific microRNAs for overexpression in N-UCMSCs and found that miR-375 and miR-26a induced IPCs differentiation from N-UCMSCs by downregulating target genes including mtpn, sox6, bhlhe22 and ccnd1. Small interfering RNAs were also used to knock down these genes in N-UCMSCs to induce the formation of IPCs. These results suggest that endogenous microRNAs involved in the formation of IPCs from adult stem cells show promise for advancing the development of an effective cell transplant therapy for diabetes. Copyright © 2017 John Wiley & Sons, Ltd.

Keywords: insulin secretion; insulin-producing cells; mesenchymal stem cells; microRNAs; small interfering RNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation / genetics
  • Chickens
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / transplantation
  • Mesenchymal Stem Cells / cytology*
  • Mice, SCID
  • MicroRNAs / metabolism*
  • Nestin / metabolism
  • RNA, Small Interfering / metabolism
  • Umbilical Cord / cytology

Substances

  • MicroRNAs
  • Nestin
  • RNA, Small Interfering