Enhanced Hepatic Differentiation of Human Induced Pluripotent Stem Cells Using Gas-Permeable Membrane

Tissue Eng Part A. 2019 Mar;25(5-6):457-467. doi: 10.1089/ten.TEA.2018.0084. Epub 2018 Dec 12.

Abstract

Although oxygen is a vital nutrient for the hepatocytes in vitro, few reports have focused on its effect during hepatic differentiation of induced pluripotent stem cells (iPSCs). In this report, we performed the hepatic differentiation of human iPSCs (hiPSCs) under different atmospheric oxygen concentrations and oxygen supply fluxes to investigate the effects of oxygen in terms of both the concentration and the supply flux. Results demonstrate that direct oxygenation through a polydimethylsiloxane (PDMS) membrane enhances the maturation and efficient production of hiPSC-derived hepatocyte-like cells (iHeps). Thus, direct oxygenation through a PDMS membrane is a better alternative culture method over conventional tissue culture-treated polystyrene (TCPS) plates for the maturation of hiPSC-derived hepatocytes in vitro.

Keywords: hepatocytes; iPS cells; oxygen; polydimethylsiloxane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / genetics
  • Albumins / metabolism
  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Cell Differentiation / drug effects*
  • Cell Membrane Permeability* / drug effects
  • Cell Respiration / drug effects
  • DNA / metabolism
  • Dimethylpolysiloxanes / pharmacology
  • Endoderm / cytology
  • GATA4 Transcription Factor / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / drug effects
  • Liver / cytology*
  • Oxygen / pharmacology*
  • Oxygen Consumption / drug effects

Substances

  • Albumins
  • Dimethylpolysiloxanes
  • GATA4 Transcription Factor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • DNA
  • Alkaline Phosphatase
  • Oxygen