期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 9, 期 10, 页码 1203-1217出版社
OXFORD UNIV PRESS
DOI: 10.1002/sctm.20-0019
关键词
cardiomyocytes; CRISPR; Cas9; electrophysiology; imaging; in vivo tracking; iPSCs; NIS; PET; rhesus macaque; sodium iodide symporter
资金
- Medical Research Scholars Program of the NIH
- Division of Intramural Research program of the NHLBI
- NCI
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZICHL006145, ZIAHL002338, ZIAHL006062] Funding Source: NIH RePORTER
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(18)F-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.
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