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Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias.
- Source :
-
Nature cardiovascular research [Nat Cardiovasc Res] 2024 Feb; Vol. 3 (2), pp. 145-165. Date of Electronic Publication: 2024 Feb 06. - Publication Year :
- 2024
-
Abstract
- Preclinical data have confirmed that human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) can remuscularize the injured or diseased heart, with several clinical trials now in planning or recruitment stages. However, because ventricular arrhythmias represent a complication following engraftment of intramyocardially injected PSC-CMs, it is necessary to provide treatment strategies to control or prevent engraftment arrhythmias (EAs). Here, we show in a porcine model of myocardial infarction and PSC-CM transplantation that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. Two unique surface marker signatures, signal regulatory protein α (SIRPA) <superscript>+</superscript> CD90 <superscript>-</superscript> CD200 <superscript>+</superscript> and SIRPA <superscript>+</superscript> CD90 <superscript>-</superscript> CD200 <superscript>-</superscript> , identify arrhythmogenic and non-arrhythmogenic cardiomyocytes, respectively. Our data suggest that modifications to current PSC-CM-production and/or PSC-CM-selection protocols could potentially prevent EAs. We further show that pharmacologic and interventional anti-arrhythmic strategies can control and potentially abolish these arrhythmias.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Humans
Disease Models, Animal
Myocardial Infarction therapy
Swine
Cells, Cultured
Cell Differentiation
Induced Pluripotent Stem Cells transplantation
Action Potentials physiology
Action Potentials drug effects
Phenotype
Biomarkers metabolism
Pluripotent Stem Cells transplantation
Stem Cell Transplantation methods
Anti-Arrhythmia Agents therapeutic use
Anti-Arrhythmia Agents pharmacology
Heart Rate physiology
Myocytes, Cardiac metabolism
Myocytes, Cardiac transplantation
Arrhythmias, Cardiac therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2731-0590
- Volume :
- 3
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nature cardiovascular research
- Publication Type :
- Academic Journal
- Accession number :
- 39196193
- Full Text :
- https://doi.org/10.1038/s44161-023-00419-3