Citations 1
CRISPR/Cas9-mediated introduction of the sodium/iodide symporter gene enables noninvasive in vivo tracking of induced pluripotent stem cell-derived cardiomyocytes
Ostrominski, John W. , Yada, Ravi Chandra , Sato, Noriko , Klein, Michael G. , Blinova, Ksenia , Valadez, Racquel, Palisoc, Maryknoll, Peng, Kah-Whye , San, Hong, Lin, Yongshun, Basuli, Falguni , Swenson, Rolf E. , Haigney, Mark C. , Boehm, Manfred , Hong, So Gun , Hong, So Gun , Dunbar, Cynthia E , Patel, Dakshesh , Pittaluga, Stefania , Zhang, Xiang , Choyke, Peter L. , Zou, Jizhong
Stem Cells Translational Medicine | July 23, 2020 | Volume: 9 | Issue: 10 | Pages: 1203-1217
Abstract Techniques that enable longitudinal tracking of cell fate after myocardial delivery are imperative for optimizing the efficacy of cell-based cardiac therapies. However, these approaches have been underutilized in preclinical models and clinical trials, and there is considerable demand for site-specific strategies achieving long-term expression of reporter genes compatible with safe noninvasive imaging. In this study, the rhesus sodium/iodide symporter (NIS) gene was incorporated into rhesus macaque induced pluripotent stem cells (RhiPSCs) via CRISPR/Cas9. Cardiomyocytes derived from NIS-RhiPSCs (NIS-RhiPSC-CMs) exhibited overall similar morphological and electrophysiological characteristics compared to parental control RhiPSC-CMs at baseline and with exposure to physiological levels of sodium iodide. Mice were injected intramyocardially with 2 million NIS-RhiPSC-CMs immediately following myocardial infarction, and serial positron emission tomography/computed tomography was performed with 18F-tetrafluoroborate to monitor transplanted cells in vivo. NIS-RhiPSC-CMs could be detected until study conclusion at 8 to 10 weeks postinjection. This NIS-based molecular imaging platform, with optimal safety and sensitivity characteristics, is primed for translation into large-animal preclinical models and clinical trials.