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使用核医学成像追踪源自人类诱导多能干细胞的移植心肌细胞。

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

作者信息

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

机构信息

Department of Cardiovascular Medicine, Okayama University Hospital, Okayama, Japan.

Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

出版信息

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

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 , which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as I, F-tetrafluoroborate (TFB), and Tc-pertechnetate (TcO), 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 TcO single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using TcO 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.

摘要

引言

移植人诱导多能干细胞衍生的心肌细胞(iPSC-CMs)是治疗心力衰竭的一种有前景的方法。移植后长期细胞植入的信息在临床上很重要。然而,尚未建立临床适用的评估方法。

方法

在本研究中,为了无创评估移植细胞的植入情况,将编码钠/碘同向转运体(NIS)的人 ,该转运体可转运放射性示踪剂,如碘(I)、氟硼酸四氟化物(TFB)和高锝酸盐(TcO),转导到人诱导多能干细胞(iPSCs)中,并使用核医学成像来追踪植入的人iPSC-CMs。

结果

为了评估表达NIS的人iPSCs的多能性,将它们皮下移植到免疫缺陷大鼠中。通过TcO单光子发射计算机断层扫描(SPECT/CT)成像检测到畸胎瘤。在纯化的人iPSC-CMs中维持了NIS表达和碘的摄取能力。使用TcO SPECT/CT成像可以随时间检测移植到免疫缺陷大鼠中的表达NIS的人iPSC-CMs。出乎意料的是,NIS表达影响人iPSCs和iPSC衍生细胞的细胞增殖。

讨论

这种功能设计的iPSC-CMs作为一种无创的移植细胞评估方法具有潜在的临床应用价值,但需要进一步研究以确定NIS转导对细胞特性和功能的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d2c/10512708/a47feca87e13/fcvm-10-1261330-g001.jpg

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