Human Cardiac Stem Cell Therapy for Heart Failure

Although human cardiac stem cell transplantation had functional benefits in the recovery in experimental myocardial infarction, the major barrier limiting its clinical application is the death of the most of the transplanted cells and poor cardiac differentiation in the host environment. Using the identical technique as clonally cell isolation from experimental animals, we generated human cardiosphere-derived cell (hCDC) enriched Es-marker genes with mesenchymal features, which were obtained from cardiac endomyocardial biopsy samples. bFGF possesses properties to promote stem cell proliferation, and formation of sufficient microvascular network created by bFGF is critical for long-term survival of transplanted donor cells. To investigate the effect of hCDC transplantation with controlled-release bFGF using biodegradable gelatin, we performed preclinical trials of chronically instrumented pigs. When combined with bFGF, hCDC transplantation specifically improved cardiac function of experimental pigs accompanied with enhancing hCDC engraftment, contributing to effective cardiovascular regeneration. Our results demonstrate a promising approach for achieving a remarkably functional cardiac repair by a combination of hCDC transplantation with bFGF-incorporating hydrogel. To verify the efficacy of this hybrid-therapy, after successful of Phase I trial, we will begin to move forward to randomized, placebo-controlled, Phase II trial using cardiac stem cell in the world for the first time.