Systematic analysis of different pluripotent stem cell-derived cardiac myocytes as potential testing model for cardiocytoprotection

Vascul Pharmacol. Oct-Nov 2020;133-134:106781. doi: 10.1016/j.vph.2020.106781. Epub 2020 Aug 19.

Abstract

Introduction: Stem cell-derived cardiac myocytes are potential sources for testing cardiocytoprotective molecules against ischemia/reperfusion injury in vitro.

Materials and methods: Here we performed a systematic analysis of two different induced pluripotent stem cell lines (iPSC 3.4 and 4.1) and an embryonic stem cell (ESC) line-derived cardiac myocytes at two different developmental stages. Cell viability in simulated ischemia/reperfusion (SI/R)-induced injury and a known cardiocytoprotective NO-donor, S-nitroso-n-acetylpenicillamine (SNAP) was tested.

Results: After analysis of full embryoid bodies (EBs) and cardiac marker (VCAM and cardiac troponin I) positive cells of three lines at 6 conditions (32 different conditions altogether), we found significant SI/R injury-induced cell death in both full EBs and VCAM+ cardiac cells at later stage of their differentiation. Moreover, full EBs of the iPS 4.1 cell line after oxidative stress induction by SNAP was protected at day-8 samples.

Conclusion: We have shown that 4.1 iPS-derived cardiomyocyte line could serve as a testing platform for cardiocytoprotection.

Keywords: Cardiocytoprotection; Cell culture; Drug screening; Embryoid body; In vitro; Induced pluripotent stem cell.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • Cell Line
  • Cell Survival / drug effects
  • Humans
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Nitric Oxide Donors / pharmacology*
  • Oxidative Stress / drug effects
  • Phenotype
  • Pluripotent Stem Cells / drug effects*
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / pathology
  • S-Nitroso-N-Acetylpenicillamine / pharmacology*
  • Troponin I / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Nitric Oxide Donors
  • Troponin I
  • Vascular Cell Adhesion Molecule-1
  • S-Nitroso-N-Acetylpenicillamine