Abstract 13480: Noninvasive Spatial and Temporal Tracking of Multilayered Cell Sheet on Infarcted Heart Using Reporter Gene Imaging
Background and aim: Transplantation of stem cell sheet is a promising strategy for the treatment of ischemic heart disease. The reporter gene imaging allows the noninvasive and serial observation of cell dynamics in vivo. The aim of this study was to investigate the feasibility of temporal and serial tracking of cell sheets on the infarcted heart using SPECT with human sodium/iodide symporter (hNIS) as a reporter gene.
Methods: Cell sheets were generated from mouse embryonic fibroblasts (MEF) derived from mice overexpressing hNIS (hNIS-Tg) (3х106 cells/sheet) using temperature-responsive dishes. Myocardial infarction was produced by ligating the left anterior descending coronary artery in F344 athymic rats. Two weeks after surgery, triple-layer cell sheets were transplated onto the infarct area (Day 0). Serial SPECT imaging was acquired after the injection of 99mTc-pertechnetate (380-660 MBq) using small animal SPECT/CT system (NanoSPECT/CT; Bioscan) at Day 1, 4, 7, 10 and 15. The histological analysis was also performed at Day4 to validate the region of high radioactivity in SPECT imaging.
Results: The significant higher uptake of 99mTc-pertechnatate in hNIS-Tg-derived MEF was confirmed in the cellular uptake study (180.1±16.6-fold vs. wild type-MEF). In the rats study, the transplanted hNIS-positive cell sheets could be observed visually as a region of high radioactivity (Figure A), and the radioactivity of cell sheets reached a peak at 40-60 minutes after isotope injection. However, the peak radioactivity of cell sheets was gradual decreased day by day (Day1: 12.84 vs. Day4: 10.68 vs. Day7: 7.73 vs. Day10: 7.27 vs. Day15: 5.92 kBq/mm3) (Figure B). The region of high radioactivity was well correlated with the histological analysis (Figure C).
Conclusion: Our results demonstrated that the reporter gene imaging with hNIS would be a useful method for the serial monitoring of transplanted cell sheets for the treatment of ischemic heart diseases.
- © 2013 by American Heart Association, Inc.