CRISPR/Cas9-mediated introduction of the sodium/iodide symporter gene enables noninvasive in vivo tracking of induced pluripotent stem cell-derived cardiomyocytes.

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 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.

journal_name

Stem Cells Transl Med

authors

Ostrominski JW,Yada RC,Sato N,Klein M,Blinova K,Patel D,Valadez R,Palisoc M,Pittaluga S,Peng KW,San H,Lin Y,Basuli F,Zhang X,Swenson RE,Haigney M,Choyke PL,Zou J,Boehm M,Hong SG,Dunbar CE

doi

10.1002/sctm.20-0019

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

1203-1217

issue

10

eissn

2157-6564

issn

2157-6580

journal_volume

9

pub_type

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