Differentiation of hepatocytes from induced pluripotent stem cells derived from human hair follicle mesenchymal stem cells

Cell Tissue Res. 2016 Oct;366(1):89-99. doi: 10.1007/s00441-016-2399-5. Epub 2016 Apr 7.

Abstract

Due to the limitations of organ donors and immune rejection in severe liver diseases, stem cell-based therapy presents a promising application for tissue repair and regeneration. As a novel cell source, mesenchymal stem cells separated from human hair follicles (HF-MSCs) are convenient to obtain and have no age limit. To date, the differentiation of HF-MSCs into hepatocytes has not been reported. In this study, we explored whether HF-MSCs and HF-MSC-derived-induced pluripotent stem cells (HF-iPS) could differentiate into hepatocytes in vitro. Flow cytometry, Oil Red O stain and Alizarin Red stain were used to identify the characteristics of HF-MSCs. The expression of liver-specific gene was detected by immunofluorescence and Quantitative Polymerase Chain Reaction. Periodic Acid-Schiff stain, Indocyanine Green stain and Low-Density Lipoprotein stain were performed to evaluate the functions of induced hepatocyte-like cells (HLCs). HF-MSCs were unable to differentiate into HLCs using previously reported procedures for MSCs from other tissues. However, HF-iPS efficiently induced the generation of HLCs that expressed hepatocyte markers and drug metabolism-related genes. HF-iPS can be used as novel and alternative cellular tools for inducing hepatocytes in vitro, simultaneously benefiting from utilizing HF-MSCs as a noninvasive and convenient cell source for reprogramming.

Keywords: End-stage liver disease; Hair follicle mesenchymal stem cells; Hepatocytes; Induced pluripotent stem cells; Multipotential differentiation.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation*
  • Cell Shape
  • Endoderm / cytology
  • Endoderm / metabolism
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hair Follicle / cytology*
  • Hep G2 Cells
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Oligonucleotide Array Sequence Analysis

Substances

  • Biomarkers