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

Autor: Ostrominski JW; Translational Stem Cell Biology Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, USA., Yada RC; Translational Stem Cell Biology Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, USA., Sato N; Molecular Imaging Program, Laboratory of Cellular Therapeutics, National Cancer Institute (NCI), NIH, Bethesda, Maryland, USA., Klein M; Division of Cardiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Blinova K; Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA., Patel D; Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA., Valadez R; Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA., Palisoc M; Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA., Pittaluga S; Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA., Peng KW; Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA., San H; Animal Surgery and Resources Core, NHLBI, NIH, Bethesda, Maryland, USA., Lin Y; iPSC Core, NHLBI, NIH, Bethesda, Maryland, USA., Basuli F; Chemistry and Synthesis Center, NHLBI, NIH, Bethesda, Maryland, USA., Zhang X; Chemistry and Synthesis Center, NHLBI, NIH, Bethesda, Maryland, USA., Swenson RE; Chemistry and Synthesis Center, NHLBI, NIH, Bethesda, Maryland, USA., Haigney M; Division of Cardiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Choyke PL; Molecular Imaging Program, Laboratory of Cellular Therapeutics, National Cancer Institute (NCI), NIH, Bethesda, Maryland, USA., Zou J; iPSC Core, NHLBI, NIH, Bethesda, Maryland, USA., Boehm M; Laboratory of Cardiovascular Regenerative Medicine, NHLBI, NIH, Bethesda, Maryland, USA., Hong SG; Translational Stem Cell Biology Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, USA., Dunbar CE; Translational Stem Cell Biology Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Jazyk: angličtina
Zdroj: Stem cells translational medicine [Stem Cells Transl Med] 2020 Oct; Vol. 9 (10), pp. 1203-1217. Date of Electronic Publication: 2020 Jul 23.
DOI: 10.1002/sctm.20-0019
Abstrakt: 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.
(© 2020 The Authors. STEM CELLS Translational Medicine published by Wiley Periodicals LLC on behalf of AlphaMed Press.)
Databáze: MEDLINE
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