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Vascular apoptosis plays a pivotal role in the development and progression of a myriad of cardiac dysfunctions, but has yet to be investigated in doxorubicin-induced cardiomyopathy (DIC). Additionally, the neovascularization potential and resulting functional consequences of embryonic stem (ES) cells and factors released from these cells in the chronic DIC myocardium remain largely unknown. To this end, we transplanted conditioned media (CM) and ES cells in the DIC-injured heart and evaluated their potential to inhibit vascular cell death, activate endogenous c-kit(+) and FLK-1(+) cells, enhance neovascularization, and augment left ventricular dysfunction. Data presented suggest transplanted CM and ES cells significantly blunt vascular cell apoptosis consequent to DIC. Quantitative immunohistochemistry data demonstrate significantly increased c-kit(+) and FLK-1(+) cells, as well as enhanced differentiated CD31(+) cells in the CM and ES cell groups relative to DIC controls. Heart function, including fractional shortening and ejection fraction, assessed by transthoracic echocardiography, was significantly improved following CM and ES cell transplantation. In conclusion, our data suggest that transplantation of CM and ES cells inhibit vascular apoptosis, activate endogenous c-kit(+) and FLK-1(+) cells and differentiate them into endothelial cells, enhance neovascularization, and improve cardiac function in the DIC-injured myocardium.

Cell therapy is emerging as a new strategy to circumvent the adverse effects of heart disease. Many experimental and clinical studies investigating the transplantation of cells into the injured myocardium have yielded promising results. Moreover, data from these reports show that transplanted stem cells can engraft within the myocardium, differentiate into major cardiac cell types, and improve cardiac function. However, results from clinical trials show conflicting results. These trials demonstrate significant improvements in cardiac function for up to 6 months. However, these improved functions were diminished when examined at 18 months. In this review, we will discuss the current literature available on cell transplantation, covering studies ranging from animal models to clinical trials.