Silvia Marchiano, Kenta Nakamura, Hans Reinecke, Lauren Neidig, Michael Lai, Shin Kadota, Filippo Perbellini, Xiulan Yang, Jordan M Klaiman, Leslie P Blakely, Elaheh Karbassi, Paul A Fields, Aidan M Fenix, Kevin M Beussman, Anu Jayabalu, Faith A Kalucki, Akiko Futakuchi-Tsuchida, Gerhard J Weber, Sarah Dupras, Hiroshi Tsuchida, Lil Pabon, Lili Wang, Björn C Knollmann, Steven Kattman, R Scott Thies, Nathan Sniadecki, W Robb MacLellan, Alessandro Bertero, Charles E Murry
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) offer a promising cell-based therapy for myocardial infarction. However, the presence of transitory ventricular arrhythmias, termed engraftment arrhythmias (EAs), hampers clinical applications. We hypothesized that EA results from pacemaker-like activity of hPSC-CMs associated with their developmental immaturity. We characterized ion channel expression patterns during maturation of transplanted hPSC-CMs and used pharmacology and genome editing to identify those responsible for automaticity in vitro...
April 6, 2023: Cell Stem Cell