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Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias. | LitMetric

AI Article Synopsis

  • - Preclinical studies show that human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) can help repair injured hearts, with multiple clinical trials underway.
  • - Ventricular arrhythmias (EAs) can occur after injecting PSC-CMs into the heart, linked to cellular diversity within the transplanted cells, particularly arrhythmogenic subpopulations like atrial and pacemaker-like cardiomyocytes.
  • - Identifying specific surface markers may help differentiate risky PSC-CMs from safer ones, and both drug treatments and other interventions can help manage or eliminate these arrhythmias in the experimental model used.

Article 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)CD90CD200 and SIRPACD90CD200, 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358004PMC
http://dx.doi.org/10.1038/s44161-023-00419-3DOI Listing

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