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

J Pálóczi; Á Szántai; J Kobolák; I Bock; E Ruivo; B Kiss; R Gáspár; J Pipis; I Ocsovszki; Z Táncos; A Fehér; A Dinnyés; Z Onódi; R Madonna; P Ferdinandy; A Görbe

doi:10.1016/j.vph.2020.106781

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

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

Authors

J Pálóczi¹, Á Szántai¹, J Kobolák², I Bock², E Ruivo¹, B Kiss³, R Gáspár¹, J Pipis⁴, I Ocsovszki¹, Z Táncos², A Fehér², A Dinnyés⁵, Z Onódi⁶, R Madonna⁷, P Ferdinandy⁸, A Görbe⁹

Affiliations

¹ Cardiovascular Research Group, Department of Biochemistry, University of Szeged, 6720 Hungary.
² Biotalentum Ltd., Gödöllő, 2100 Hungary.
³ Cardiovascular Research Group, Department of Biochemistry, University of Szeged, 6720 Hungary; MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, 1085 Hungary.
⁴ Pharmahungary Group, Szeged, 6722 Hungary.
⁵ Biotalentum Ltd., Gödöllő, 2100 Hungary; Molecular Animal Biotechnology Laboratory, Szent István University, Gödöllő, 2100 Hungary.
⁶ MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, 1085 Hungary.
⁷ Institute of Cardiology, Department of Surgical, Medical and Molecular Pathology and Critical Area Medicine, University of Pisa, 56124 Pisa; Internal Medicine, Cardiology Division, University of Texas Medical School in Houston, Houston, Texas.
⁸ Cardiovascular Research Group, Department of Biochemistry, University of Szeged, 6720 Hungary; Pharmahungary Group, Szeged, 6722 Hungary; MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, 1085 Hungary; Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Szeged, 6720, Hungary.
⁹ Cardiovascular Research Group, Department of Biochemistry, University of Szeged, 6720 Hungary; Pharmahungary Group, Szeged, 6722 Hungary; MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, 1085 Hungary; Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Szeged, 6720, Hungary. Electronic address: gorbe.aniko@med.semmelweis-univ.hu.

PMID: 32827678
DOI: 10.1016/j.vph.2020.106781

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