Abstract 3254: Rhesus Monkey Derived Cardiospheres (CSps) for Myocardial Restoration After LAD Ligation in Mice
Recently, resident cardiac stem cells have been isolated and expanded in vitro, where they form large cell clusters termed “cardiospheres” (CSps). They differentiate into cardiomyocytes in vitro and might be a promising autologous cell source for cardiac restoration. The aim of this study was to determine the cell survival and functional effects of Rhesus monkey cardiosphere derived cells (CDCs) in a mouse model of myocardial infarction (MI). Cardiospheres derived from Rhesus monkeys were cultured and expanded in vitro and CDCs were injected intramyocardially into immunodeficient SCID beige mice after LAD ligature (MI group: n=20). MI animals were either treated with placebo (N=10) or CDCs (N=10; 1,0×10^6 cells). They underwent conductance catheter (CC) evaluation to determine functional cardiac outcome (e.g. left ventricular ejection fraction=LV-EF; maximum rate of LV pressure increase=dP/dtmax) after one or four weeks postoperatively (each group N=5) and were afterwards sacrificed for histological evaluation. LAD ligature resulted in a significantly reduced myocardial function compared to non-infarct controls (LV-EF 64,59% vs. 23,00%, p<0,05). CDC grafts could be identified in all transplanted animals one and four weeks after cell transplantation. After 4 weeks we identified more than 25% of the transplanted cells. Cell proliferation was detectable until one week after the procedure by immunohistochemical staining for Ki67. The characterization of the CDC grafts (e.g. cardiospecific markers) is currently under investigation. Functional parameters determined by CC evaluation tended to improve with cell therapy after 4weeks (LV-EF placebo 21,4% vs. LV-EF cell therapy 29,7%; dP/dt max placebo 3642mmHg/sec vs. dP/dt max cell therapy 4334mmHg/sec; n.s.). For the first time, Rhesus cardiosphere derived cells (CDCs) have been used to restore infarcted myocardium in an animal model. The cells proliferated in vivo, survived until 4 weeks after grafting and apparently improved heart function as determined by conductance catheter evaluation. Cardiosphere derived cells appear to be a promising cell source for myocardial regeneration. Further investigation is warranted to develop therapeutic applications in patients.