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DOI: 10.1055/s-0029-1246792
Rhesus monkey derived „cardiospheres“ (CSps) for cardiac regenerative therapy in a mouse infarct model
Resident cardiac stem cells have been isolated and expanded in vitro. They form large cell clusters termed "cardiospheres" (CSps), differentiate into cardiomyocytes in vitro and might be a promising autologous cell source for cardiac restoration. The aim of this study was to determine cell survival and functional effects of Rhesus monkey cardiosphere derived cells (CDCs) in a mouse myocardial infarction model (MI).
Cardiospheres derived from Rhesus monkeys were expanded in vitro and either CDCs (1.0×106) or placebo were injected intramyocardially into immunodeficient SCID beige mice after LAD ligature (each group N=10). All animals underwent conductance catheter (CC) evaluation to determine functional cardiac outcome (each group N=5).
LAD ligature resulted in a significantly reduced myocardial function compared to non-infarct controls (LV-EF 64% vs. 23%, p<0.05). CDC grafts could be identified in all animals after cell transplantation. Cell proliferation was detectable until one week as determined 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% vs. LV-EF CDC 30%; n.s.).
For the first time, Rhesus 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.