Dataset Information

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

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.

SUBMITTER: Saito Y

PROVIDER: S-EPMC10512708 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

<i>In vivo</i> tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging.

Saito Yukihiro Y Nose Naoko N Iida Toshihiro T Akazawa Kaoru K Kanno Takayuki T Fujimoto Yuki Y Sasaki Takanori T Akehi Masaru M Higuchi Takahiro T Akagi Satoshi S Yoshida Masashi M Miyoshi Toru T Ito Hiroshi H Nakamura Kazufumi K

Frontiers in cardiovascular medicine 20230907

<h4>Introduction</h4>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.<h4>Methods</h4>In this study, to noninvasively assess transplanted cell engraftment, human <i>SLC5A5</i>, which encodes a sodium/iodide symporter (NIS) that transports radioact ...[more]

PMID: 37745108

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Project description:BackgroundInduced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are regarded as promising cell type for cardiac cell replacement therapy, but it is not known whether the developmental stage influences their persistence and functional integration in the host tissue, which are crucial for a long-term therapeutic benefit. To investigate this, we first tested the cell adhesion capability of murine iPSC-CM in vitro at three different time points during the differentiation process and then examined cell persistence and quality of electrical integration in the infarcted myocardium in vivo.MethodsTo test cell adhesion capabilities in vitro, iPSC-CM were seeded on fibronectin-coated cell culture dishes and decellularized ventricular extracellular matrix (ECM) scaffolds. After fixed periods of time, stably attached cells were quantified. For in vivo experiments, murine iPSC-CM expressing enhanced green fluorescent protein was injected into infarcted hearts of adult mice. After 6-7 days, viable ventricular tissue slices were prepared to enable action potential (AP) recordings in transplanted iPSC-CM and surrounding host cardiomyocytes. Afterwards, slices were lysed, and genomic DNA was prepared, which was then used for quantitative real-time PCR to evaluate grafted iPSC-CM count.ResultsThe in vitro results indicated differences in cell adhesion capabilities between day 14, day 16, and day 18 iPSC-CM with day 14 iPSC-CM showing the largest number of attached cells on ECM scaffolds. After intramyocardial injection, day 14 iPSC-CM showed a significant higher cell count compared to day 16 iPSC-CM. AP measurements revealed no significant difference in the quality of electrical integration and only minor differences in AP properties between d14 and d16 iPSC-CM.ConclusionThe results of the present study demonstrate that the developmental stage at the time of transplantation is crucial for the persistence of transplanted iPSC-CM. iPSC-CM at day 14 of differentiation showed the highest persistence after transplantation in vivo, which may be explained by a higher capability to adhere to the extracellular matrix.