Genetic labeling of human endothelial progenitor cells by use of the sodium-iodide symporter gene for in vivo imaging of cardiac cell transplantation

Abstract

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Objectives: Intramyocardial progenitor cell transplantation is considered a promising therapy for cardiac regeneration. Genetic labeling with a reporter gene may provide answers to unresolved questions concerning cell engraftment. We sought to test the feasibility of the human sodium/iodine symporter gene (hNIS) for this purpose.

Methods: Human endothelial progenitor cells (EPC) were stably transfected with hNIS using a retroviral vector (RvNIS-EPC) in conjunction with LacZ for histological confirmation. Specific radiotracer uptake, preserved cell viability and normal proliferation capacity were demonstrated in vitro. In nude rats, 4 million RvNIS-EPC were subsequently injected intramyocardially following thoracotomy (n=8). EPC transduced with NIS using adenoviral vector (AdNIS-EPC) (n=9) and EPC non-transfected with hNIS (nonNIS-EPC) (n=6) were used as control. One day after the transplantation, 18.5 MBq of I-124 were administrated via tail vein for small animal PET (Philips Mosaic scanner; absolute sensitivity equals 0.65 %) and autoradiography.

Results: Postmortem autoradiography showed elevated regional radioactivity in RvNIS-EPC and AdNIS-EPC injected myocardium, which was absent in nonNIS-EPC injected animals (uptake ratio: 3.9+/-3.6 and 3.2+/-2.5 vs 1.2+/-0.2; p<0.05). Presence of transplanted cells was confirmed by LacZ staining, and the area of stained cells correlated with autoradiographic I-124 uptake (r = 0.76, p<.0001). In vivo PET imaging, however, yielded variable results. Focal myocardial I-124 uptake was unequivocally observed in only 2 RvNIS-EPC injected rats and 2 AdNIS-EPC injected rats.

Conclusions: Non-invasive assessment of localization and viability of transplanted EPCs using genetic labeling with hNIS remains a methodological challenge. In our model, a varying amount of viable cells was present at the time of imaging. Lack of in vivo signal for smaller cell numbers despite ex vivo cell detection emphasizes the need for strategies to increase sensitivity of PET imaging.