ArticleStem cell research & therapy2015
Susceptibility of murine induced pluripotent stem cell-derived cardiomyocytes to hypoxia and nutrient deprivation.
Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Guidelines for experimental models of myocardial ischemia and infarction.American journal of physiology. Heart and circulatory physiology · 2018Guideline
- ROS-Mediated Cardiomyocyte Proliferation and Myocardial Regeneration: Mechanisms and Targeted Strategies for Ischemic Heart Disease.Journal of cardiovascular development and disease · 2026Review
- Angiogenic Cell Precursors and Neural Cell Precursors in Service to the Brain-Computer Interface.Cells · 2025Review
- Cardioprotection by poloxamer 188 is mediated through increased endothelial nitric oxide production.Scientific reports · 2025Article
- Maturation of pluripotent stem cell-derived cardiomyocytes: limitations and challenges from metabolic aspects.Stem cell research & therapy · 2024Review
- Differential Effects of Beta-Hydroxybutyrate Enantiomers on Induced Pluripotent Stem Derived Cardiac Myocyte Electrophysiology.Biomolecules · 2022Article
- Pre-Conditioning Methods and Novel Approaches with Mesenchymal Stem Cells Therapy in Cardiovascular Disease.Cells · 2022Review
- Beclin-1/LC3-II dependent macroautophagy was uninfluenced in ischemia-challenged vascular endothelial cells.Genes & diseases · 2022Article
- Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure.Regenerative therapy · 2021Article
- Surfing the clinical trials of mesenchymal stem cell therapy in ischemic cardiomyopathy.Stem cell research & therapy · 2021Review
- Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage.Frontiers in cardiovascular medicine · 2021Article
- The effect of hypoxia on the proteomic signature of pig adipose-derived stromal/stem cells (pASCs).Scientific reports · 2020Article
- Roles of Reactive Oxygen Species in Cardiac Differentiation, Reprogramming, and Regenerative Therapies.Oxidative medicine and cellular longevity · 2020Review
- Pleiotropic roles of autophagy in stem cell-based therapies.Cytotherapy · 2019Review
- Sevoflurane prevents hypoxia/reoxygenation-induced cardiomyocyte apoptosis by inhibiting PI3KC3-mediated autophagy.Human cell · 2019Article
- Chaperones and Beyond as Key Players in Pluripotency Maintenance.Frontiers in cell and developmental biology · 2019Review
- Mesenchymal Stem Cell-Based Therapy for Cardiovascular Disease: Progress and Challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Review
- Early Postnatal Cardiomyocyte Proliferation Requires High Oxidative Energy Metabolism.Scientific reports · 2017Article
- MicroRNA-210 suppresses glucocorticoid receptor expression in response to hypoxia in fetal rat cardiomyocytes.Oncotarget · 2017Article
- The cytoprotective capacity of processed human cardiac extracellular matrix.Journal of materials science. Materials in medicine · 2016Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionInduced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) may be suitable for myocardial repair. While their functional and structural properties have been extensively investigated, their response to ischemia-like conditions has not yet been clearly defined.
methodsiPS-CMs were differentiated and enriched from murine induced pluripotent stem cells expressing enhanced green fluorescent protein (eGFP) and puromycin resistance genes under the control of an α-myosin heavy chain (α-MHC) promoter. iPS-CMs maturity and function were characterized by microscopy, real-time PCR, calcium transient recordings, electrophysiology, and mitochondrial function assays, and compared to those from neonatal murine cardiomyocytes. iPS-CMs as well as neonatal murine cardiomyocytes were exposed for 3 hours to hypoxia (1% O2) and glucose/serum deprivation, and viability, apoptosis markers, reactive oxygen species, mitochondrial membrane potential and intracellular stress signaling cascades were investigated. Then, the iPS-CMs response to mesenchymal stromal cell-conditioned medium was determined.
resultsiPS-CMs displayed key morphological and functional properties that were comparable to those of neonatal cardiomyocytes, but several parameters indicated an earlier iPS-CMs maturation stage. During hypoxia and glucose/serum deprivation, iPS-CMs exhibited a significantly higher proportion of poly-caspase-active, 7-aminoactinomycin D-positive and TUNEL-positive cells than neonatal cardiomyocytes. The average mitochondrial membrane potential was reduced in "ischemic" iPS-CMs but remained unchanged in neonatal cardiomyocytes; reactive oxygen species production was only increased in "ischemic" iPS-CMs, and oxidoreductase activity in iPS-CMs dropped more rapidly than in neonatal cardiomyocytes. In iPS-CMs, hypoxia and glucose/serum deprivation led to upregulation of Hsp70 transcripts and decreased STAT3 phosphorylation and total PKCε protein expression. Treatment with mesenchymal stromal cell-conditioned medium preserved oxidoreductase activity and restored pSTAT3 and PKCε levels.
conclusioniPS-CMs appear to be particularly sensitive to hypoxia and nutrient deprivation. Counteracting the ischemic susceptibility of iPS-CMs with mesenchymal stromal cell-conditioned medium may help enhance their survival and efficacy in cell-based approaches for myocardial repair.
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