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

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1261330

DOI=10.3389/fcvm.2023.1261330

ISSN=2297-055X

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>In this study, to noninvasively assess transplanted cell engraftment, human <italic>SLC5A5</italic>, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as <sup>125</sup>I, <sup>18</sup>F-tetrafluoroborate (TFB), and <sup>99m</sup>Tc-pertechnetate (<sup>99m</sup>TcO<sub>4</sub><sup>−</sup>), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.</p></sec><sec><title>Results</title><p>To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by <sup>99m</sup>TcO<sub>4</sub><sup>−</sup> single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of <sup>125</sup>I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using <sup>99m</sup>TcO<sub>4</sub><sup>−</sup> SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.</p></sec><sec><title>Discussion</title><p>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.</p></sec>