Selvakumar, Dinesh and Clayton, Zoe E. and Prowse, Andrew and Dingwall, Steve and Kim, Sul Ki and Reyes, Leila and George, Jacob and Shah, Haisam and Chen, Siqi and Leung, Halina H. L. and Hume, Robert D. and Tjahjadi, Laurentius and Igoor, Sindhu and Skelton, Rhys J. P. and Hing, Alfred and Paterson, Hugh and Foster, Sheryl L. and Pearson, Lachlan and Wilkie, Emma and Marcus, Alan D. and Jeyaprakash, Prajith and Wu, Zhixuan and Chiu, Han Shen and Ongtengco, Cherica Felize J. and Mulay, Onkar and McArthur, Jeffrey R. and Barry, Tony and Lu, Juntang and Tran, Vu and Bennett, Richard and Kotake, Yasuhito and Campbell, Timothy and Turnbull, Samual and Gupta, Anunay and Nguyen, Quan and Ni, Guiyan and Grieve, Stuart M. and Palpant, Nathan J. and Pathan, Faraz and Kizana, Eddy and Kumar, Saurabh and Gray, Peter P. and Chong, James J. H. (2024) Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias. Nature Cardiovascular Research, 3 (2). pp.145-165. ISSN 2731-0590
Full text not available from this repository.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 alpha (SIRPA)(+)CD90(-)CD200(+) and SIRPA(+)CD90(-)CD200(-), 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.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 29 Dec 2024 06:26 |
| Last Modified: | 29 Dec 2024 06:26 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1595 |
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