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

John W. Ostrominski, Ravi Chandra Yada, Noriko Sato, Michael Klein, Ksenia Blinova, Dakshesh Patel, Racquel Valadez, Maryknoll Palisoc, Stefania Pittaluga, Kah Whye Peng, Hong San, Yongshun Lin, Falguni Basuli, Xiang Zhang, Rolf E. Swenson, Mark Haigney, Peter L. Choyke, Jizhong Zou, Manfred Boehm, So Gun HongCynthia E. Dunbar

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalStem Cells Translational Medicine
DOIs
StateAccepted/In press - 2020

Keywords

  • cardiomyocytes
  • CRISPR/Cas9
  • electrophysiology
  • imaging
  • in vivo tracking
  • iPSCs
  • NIS
  • PET
  • rhesus macaque
  • sodium iodide symporter

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'CRISPR/Cas9-mediated introduction of the sodium/iodide symporter gene enables noninvasive in vivo tracking of induced pluripotent stem cell-derived cardiomyocytes'. Together they form a unique fingerprint.

  • Cite this

    Ostrominski, J. W., Yada, R. C., Sato, N., Klein, M., Blinova, K., Patel, D., Valadez, R., Palisoc, M., Pittaluga, S., Peng, K. W., San, H., Lin, Y., Basuli, F., Zhang, X., Swenson, R. E., Haigney, M., Choyke, P. L., Zou, J., Boehm, M., ... Dunbar, C. E. (Accepted/In press). CRISPR/Cas9-mediated introduction of the sodium/iodide symporter gene enables noninvasive in vivo tracking of induced pluripotent stem cell-derived cardiomyocytes. Stem Cells Translational Medicine. https://doi.org/10.1002/sctm.20-0019