Cardiac regenerative therapy integrated via human autologous cardiac stem cell and biodegradable bFGF-incorporating gelatin hydrogel

Although patients with refractory heart failure have only poor prognosis without heart transplantation, limited donors could not rescue them. However, the limited success in clinical trials of cell therapy for cardiac repair leads to the disagreements in the interpretation of the efficacy of cell therapy. Using the identical technique as clonally cell isolation from experimental animals, we generated human cardiac stem cell (hCSC) enriched Es-marker genes with mesenchymal features, which were obtained from cardiac endomyocardial biopsy samples. To investigate the effect of an integrated biotherapy via hCSC transplantation with controlled-release bFGF using biodegradable gelatin, we performed two randomized, controlled trials of chronically instrumented pigs, which were randomly assigned to receive placebo or bFGF hydrogel-sheet implantation combined with or without hCSCs and human bone marrow stem cell (hBMC) transplantation. At 1 month after intervention, the absolute change in LV function was significantly greater in the bFGF group (3.6%) than placebo. When combined with cell transplantation, bFGF specifically improved cardiac function in hCSC (13%) rather than hBMC-injected hearts (3.8%) and enhanced hCSC engraftment, contributing to effective cardiovascular regeneration. Our findings suggest that controlled delivery of bFGF may improve hCSC survival and alter post-ischemic microenvironment to optimize hCSC therapy. This novel integrated-strategy demonstrates significantly functional improvements after myocardial infarction, and may potentially represent a therapeutic approach to be phase I/IIa trialed in human heart failure.