Spatial and temporal tracking of multi-layered cells sheet using reporter gene imaging with human sodium iodide symporter: a preclinical study using a rat model of myocardial infarction - UTU Research Portal

A1 Refereed original research article in a scientific journal

Spatial and temporal tracking of multi-layered cells sheet using reporter gene imaging with human sodium iodide symporter: a preclinical study using a rat model of myocardial infarction

Authors: Otani, Kentaro; Zeniya, Tsutomu; Kawashima, Hidekazu; Moriguchi, Tetsuaki; Nakano, Atsushi; Han, Chunlei; Murata, Shunsuke; Nishimura, Kunihiro; Koshino, Kazuhiro; Yamahara, Kenichi; Inubushi, Masayuki; Iida, Hidehiro

Publisher: SPRINGER

Publishing place: NEW YORK

Publication year: 2024

Journal: European Journal of Nuclear Medicine and Molecular Imaging

Journal name in source: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING

Journal acronym: EUR J NUCL MED MOL I

Volume: 52

Issue: 1

First page : 74

Last page: 87

Number of pages: 14

ISSN: 1619-7070

eISSN: 1619-7089

DOI: https://doi.org/10.1007/s00259-024-06889-2

Web address : https://doi.org/10.1007/s00259-024-06889-2

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/457846419

Abstract

Purpose

This study aimed to evaluate a novel technique for cell tracking by visualising the activity of the human sodium/iodide symporter (hNIS) after transplantation of hNIS-expressing multilayered cell sheets in a rat model of chronic myocardial infarction.

Methods

Triple-layered cell sheets were generated from mouse embryonic fibroblasts (MEFs) derived from mice overexpressing hNIS (hNIS-Tg). Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery in F344 athymic rats, and a triple-layered MEFs sheets were transplanted to the infarcted area two weeks after surgery. To validate the temporal tracking and kinetic analysis of the transplanted MEFs sheets, sequential cardiac single-photon emission computed tomography (SPECT) examinations with a 99mTcO4- injection were performed. The cell sheets generated using MEFs of wild-type mice (WT) served as controls.

Results

A significantly higher amount of 99mTcO4- was taken into the hNIS-Tg MEFs than into WT MEFs (146.1 +/- 30.9-fold). The obvious accumulation of 99mTcO4- was observed in agreement with the region where hNIS-Tg MEFs were transplanted, and these radioactivities peaked 40-60 min after 99mTcO4- administration. The volume of distribution of the hNIS-Tg MEF sheets declined gradually after transplantation, implying cellular malfunction and a loss in the number of transplanted cells.

Conclusion

The reporter gene imaging with hNIS enables the serial tracking and quantitative kinetic analysis of cell sheets transplanted to infarcted hearts.

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s00259-024-06889-2.pdf

Funding information in the publication:
Open Access funding provided by University of Turku (including Turku University Central Hospital). This study was funded by JSPS KAKENHI Grant Number JP26293282 (to MI, KO, and KY) and by the Japan Cardiovascular Research Foundation (#12 − 003 to HI), and research grants from the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP19mk0101099 (to KO) and 15jm0310001 (to HI).