Stem Cell Engraftment in A Heterotopic Cardiac Hamster-To-Rat Xenotransplantation Model

P1102 Aims: The aim of the present study was to demonstrate in a rat cardiac allotransplantation model the capacity of progenitor stem cells to engraft the transplanted heart and transdifferentiate into cardiomyocytes. Methods: A heterotopic cardiac transplantation procedure was performed between wild-type Sprague-Dawley rats (Harlan Italia) which served as source of organs, and green fluorescent protein (GFP) Sprague-Dawley transgenic rats (Japan SLC) used as recipients. Graft cold ischemia time was 30 minutes (n=7) or 240 minutes(n=12). Recipients were treated by intramuscular cyclosporine A (Novartis) at a dose of 10mg/kg/day throughout the postoperative period. The transplanted hearts were harvested on postoperative day 15 or ≥90 and analyzed histologically and for the presence of GFP positive cells. Native hearts served as controls. The GFP positive cells were characterized for specific muscle differentiation markers and analyzed with immunofluoresence and confocal microscopy. Results: A high number of GFP positive cells were found in the transplanted hearts, mostly associated with inflammatory cells. In our hands, no difference was observed between organs preserved at different ischemia times and grafts harvested on postoperative day 15, or in long-surviving grafts. In 10/19 (53%) of the organs analyzed, GFP positive cells with shape and morphology compatible with that of mature cardiomyocytes were found. These cells expressed cardiomyocyte-specific markers such as desmin, troponin I, cardiac myosin heavy chain and connexin 43 and were localized mainly at the border zone between well-preserved cardiomyocytes and areas of tissue damage. Occasionally, small GFP positive cells expressing GATA-4 were also found. Conclusions: A heterotopic cardiac allotransplantation model in the rat is a powerful animal model to study stem cells engraftment in damaged hearts. Our preliminary data suggest that stem cells can engraft the transplanted heart and, possibly, differentiate into cardiomyocytes. Fusion versus transdifferentiation events are currently under examination.