Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias.
Myocytes, Cardiac
/ metabolism
Animals
Arrhythmias, Cardiac
/ therapy
Humans
Disease Models, Animal
Myocardial Infarction
/ therapy
Swine
Cells, Cultured
Cell Differentiation
Induced Pluripotent Stem Cells
/ transplantation
Action Potentials
/ physiology
Phenotype
Biomarkers
/ metabolism
Pluripotent Stem Cells
/ transplantation
Stem Cell Transplantation
/ methods
Anti-Arrhythmia Agents
/ therapeutic use
Heart Rate
/ physiology
Journal
Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676
Informations de publication
Date de publication:
Feb 2024
Feb 2024
Historique:
received:
06
12
2022
accepted:
26
12
2023
medline:
28
8
2024
pubmed:
28
8
2024
entrez:
28
8
2024
Statut:
ppublish
Résumé
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)
Identifiants
pubmed: 39196193
doi: 10.1038/s44161-023-00419-3
pii: 10.1038/s44161-023-00419-3
doi:
Substances chimiques
Biomarkers
0
Anti-Arrhythmia Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
145-165Subventions
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : APP1194139/APP1126276
Organisme : National Heart Foundation of Australia (Heart Foundation)
ID : 101889
Informations de copyright
© 2024. The Author(s).
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