In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging

Yukihiro Saito; Naoko Nose; Toshihiro Iida; Kaoru Akazawa; Takayuki Kanno; Yuki Fujimoto; Takanori Sasaki; Masaru Akehi; Takahiro Higuchi; Satoshi Akagi; Masashi Yoshida; Toru Miyoshi; Hiroshi Ito; Kazufumi Nakamura

doi:10.3389/fcvm.2023.1261330

In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging

Front Cardiovasc Med. 2023 Sep 7:10:1261330. doi: 10.3389/fcvm.2023.1261330. eCollection 2023.

Authors

Yukihiro Saito¹, Naoko Nose², Toshihiro Iida³, Kaoru Akazawa³, Takayuki Kanno², Yuki Fujimoto², Takanori Sasaki⁴, Masaru Akehi⁴, Takahiro Higuchi^{2

5

6}, Satoshi Akagi⁷, Masashi Yoshida⁸, Toru Miyoshi⁷, Hiroshi Ito⁹, Kazufumi Nakamura⁷

Affiliations

¹ Department of Cardiovascular Medicine, Okayama University Hospital, Okayama, Japan.
² Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
³ Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
⁴ Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
⁵ Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
⁶ Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany.
⁷ Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
⁸ Department of Chronic Kidney Disease and Cardiovascular Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
⁹ Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan.

Abstract

Introduction: Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established.

Methods: In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as ¹²⁵I, ¹⁸F-tetrafluoroborate (TFB), and ^99mTc-pertechnetate (^99mTcO₄^-), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.

Results: To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by ^99mTcO₄^- single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of ¹²⁵I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using ^99mTcO₄^- SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.

Discussion: Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions.

Keywords: cell-based therapy; human induced pluripotent stem cell-derived cardiomyocytes; in vivo imaging; single photon emission computed tomography; sodium/iodide symporter.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article.