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

Abstract

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.