Universität zu Köln

Peters, Marijn C., Maas, Renee G. C., van Adrichem, Iris, Doevendans, Pieter A. M., Mercola, Mark, Saric, Tomo, Buikema, Jan W., van Mil, Alain, Chamuleau, Steven A. J., Sluijter, Joost P. G., Hnatiuk, Anna P. and Neef, Klaus (2022). Metabolic Maturation Increases Susceptibility to Hypoxia-induced Damage in Human iPSC-derived Cardiomyocytes. Stem Cells Transl. Med., 11 (10). S. 1040 - 1052. OXFORD: OXFORD UNIV PRESS. ISSN 2157-6580

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Abstract

The development of new cardioprotective approaches using in vivo models of ischemic heart disease remains challenging as differences in cardiac physiology, phenotype, and disease progression between humans and animals influence model validity and prognostic value. Furthermore, economical and ethical considerations have to be taken into account, especially when using large animal models with relevance for conducting preclinical studies. The development of human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has opened new opportunities for in vitro studies on cardioprotective compounds. However, the immature cellular phenotype of iPSC-CMs remains a roadblock for disease modeling. Here, we show that metabolic maturation renders the susceptibility of iPSC-CMs to hypoxia further toward a clinically representative phenotype. iPSC-CMs cultured in a conventional medium did not show significant cell death after exposure to hypoxia. In contrast, metabolically matured (MM) iPSC-CMs showed inhibited mitochondrial respiration after exposure to hypoxia and increased cell death upon increased durations of hypoxia. Furthermore, we confirmed the applicability of MM iPSC-CMs for in vitro studies of hypoxic damage by validating the known cardioprotective effect of necroptosis inhibitor necrostatin-1. Our results provide important steps to improving and developing valid and predictive human in vitro models of ischemic heart disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Peters, Marijn C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Maas, Renee G. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Adrichem, Iris UNSPECIFIED UNSPECIFIED UNSPECIFIED Doevendans, Pieter A. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mercola, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Saric, Tomo UNSPECIFIED UNSPECIFIED UNSPECIFIED Buikema, Jan W. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Mil, Alain UNSPECIFIED UNSPECIFIED UNSPECIFIED Chamuleau, Steven A. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sluijter, Joost P. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hnatiuk, Anna P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Neef, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-681194
DOI:	10.1093/stcltm/szac061
Journal or Publication Title:	Stem Cells Transl. Med.
Volume:	11
Number:	10
Page Range:	S. 1040 - 1052
Date:	2022
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	2157-6580
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SIGNALING CONTROLS; HUMAN HEART; MOUSE; CARDIOPROTECTION; DIFFERENTIATION; EXPRESSION; PROTEINS; DISEASE; INJURY; CELLS Multiple languages Cell & Tissue Engineering Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68119