Evidence map›Paper›PMID 36018047›Full record

ArticleStem cells translational medicine2022

Metabolic Maturation Increases Susceptibility to Hypoxia-induced Damage in Human iPSC-derived Cardiomyocytes.

Marijn C Peters, Renee G C Maas, Iris van Adrichem, Pieter A M Doevendans, Mark Mercola, Tomo Šarić, Jan W Buikema, Alain van Mil, Steven A J Chamuleau, Joost P G Sluijter and 2 more

Erratum issuedAbstract read
In one paragraph

Article in Stem cells translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Marijn C PetersDepartment of Cardiology, Laboratory of Experimental Cardiology, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.
Renee G C MaasDepartment of Cardiology, Laboratory of Experimental Cardiology, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.
Iris van AdrichemDepartment of Cardiology, Laboratory of Experimental Cardiology, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.
Pieter A M DoevendansDepartment of Cardiology, Laboratory of Experimental Cardiology, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.ORCID 0000-0002-6257-7169
Mark MercolaCardiovascular Institute and Department of Medicine, Stanford University, Stanford, CA, USA.ORCID 0000-0002-1430-2013
Tomo ŠarićCenter for Physiology and Pathophysiology, Institute for Neurophysiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Jan W BuikemaDepartment of Cardiology, Laboratory of Experimental Cardiology, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.
Alain van MilDepartment of Cardiology, Laboratory of Experimental Cardiology, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.ORCID 0000-0001-9906-5047
Steven A J ChamuleauDepartment of Cardiology, Laboratory of Experimental Cardiology, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.
Joost P G SluijterDepartment of Cardiology, Laboratory of Experimental Cardiology, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.
Anna P HnatiukCardiovascular Institute and Department of Medicine, Stanford University, Stanford, CA, USA.
Klaus NeefDepartment of Cardiology, Laboratory of Experimental Cardiology, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.ORCID 0000-0001-8271-6552

Funding

Project 3 (Mercola)P01HL141084 · NHLBI · STANFORD UNIVERSITY · PI Joseph C. Wu · 2019 to 2026
$21.1M
Targeting the genotype to phenotype link in HCM as a therapeutic strategyR01HL152055 · NHLBI · STANFORD UNIVERSITY · PI MERCOLA, MARK · 2021 to 2024
$2.3M
European Research Council 725229NHLBI NIH HHS P01 HL141084NHLBI NIH HHS R01 HL152055NIH HHS 5P01HL141084
6 · The paper itself

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.

Indexed as

Induced Pluripotent Stem CellsMyocardial IschemiaAnimalsCell DifferentiationHumansHypoxiaMyocytes, Cardiaccardiomyocytesdamagehypoxiainduced pluripotent stem cells (iPSC)ischemiametabolic maturation

Identifiers

PMID36018047
PMCPMC9585948

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.