Differentiation of umbilical cord derived mesenchymal stem cells to hepatocyte cells by transfection of miR-106a, miR-574-3p, and miR-451

Gene. 2018 Aug 15:667:1-9. doi: 10.1016/j.gene.2018.05.028. Epub 2018 May 12.

Abstract

Studying the profile of micro RNAs (miRs) elucidated the highest expressed miRs in hepatic differentiation. In this study, we investigated to clarify the role of three embryonic overexpressed miRs (miR-106a, miR-574-3p and miR-451) during hepatic differentiation of human umbilical cord derived mesenchymal stem cells (UC-MSCs). We furthermore, aimed to explore whether overexpression of any of these miRs alone is sufficient to induce the differentiation of the UC-MSCs into hepatocyte-like cells. UC-MSCs were transfected either alone or together with miR-106a, miR-574-3p and miR-451 and their potential hepatic differentiation and alteration in gene expression profile, morphological changes and albumin secretion ability were investigated. We found that up-regulation of any of these three miRs alone cannot induce expression of all hepatic specific genes. Transfection of each miR alone, led to Sox17, FoxA2 expression that are related to initiation step of hepatic differentiation. However, concurrent ectopic overexpression of three miRs together can induce UC-MSCs differentiation into functionally mature hepatocytes. These results show that miRs have the capability to directly convert UC-MSCs to a hepatocyte phenotype in vitro.

Keywords: Hepatocyte differentiation; Micro RNA; Tissue engineering; Umbilical cord derived mesenchymal stem cells.

MeSH terms

  • Cell Differentiation
  • Cells, Cultured
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Hepatocyte Nuclear Factor 3-beta / genetics
  • Hepatocytes / cytology*
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • MicroRNAs / genetics*
  • SOXF Transcription Factors / genetics
  • Transfection
  • Umbilical Cord / cytology*

Substances

  • FOXA2 protein, human
  • MIRN106 microRNA, human
  • MIRN451 microRNA, human
  • MIRN574 microRNA, human
  • MicroRNAs
  • SOX17 protein, human
  • SOXF Transcription Factors
  • Hepatocyte Nuclear Factor 3-beta