Abstract 424: Controlled Intramyocardial-delivery Of Basic Fibroblast Growth Factor Combined With Human Cardiac Stem Cell Transplantation In Chronic Myocardial Infarction: A Randomized Controlled Preclinical-trial
Background: Although the prospect of regenerating new myocardial tissue by using cardiac stem cell (CSC) therapies provided a great excitement, recent studies have questioned the ability of CSCs to effectively generate cardiomyocytes without long-term engraftment and differentiation. In this study, we investigated whether controlled release of basic fibroblast growth factor (bFGF) to CSCs as well as post-ischemic environment might improve the transplanted cell survival and function.
Methods: Human heart tissues were obtained from right ventricle of 10 patients and individual CSCs were isolated by serial passage to enrich mesenchymal cell population expressing NKX 2–5. Biodegradable bFGF-incorporating hydrogel sheet was prepared through chemical crosslinking gelatin and was impregnated with human recombinant bFGF. Myocardial infarctions were induced in immunosuppressed 60 pigs by 90 min balloon occlusion of the LAD, and they were randomly assigned to receive intramyocardial injection of placebo-medium or bFGF sheet implantation combined with or without human CSCs (2 doses) or independent human clones of bone marrow stem cell (BMC) transplantation 4 weeks after reperfusion.
Results: At 1 month, the absolute change in the LV function was significantly greater in the bFGF group than in the placebo group (MRI:+ 3.8 ± 1.4 vs −0.4 ± 1.9 %, p<0.005), that was associated with enhanced myocardial perfusion (+30.9 ± 8.4 vs −14.5 ± 8.2 %, p<0.05). When combined with cell transplantation, bFGF exerted cell-type specific additive-effects on functional recovery (+8.4 ± 0.8 in 2x107 CSCs vs+2.6 ± 1.8 % in 2x107 BMCs, p<0.01). These beneficial effects of bFGF were not evident in spared 2x108 CSCs transplantation accompanied by dense accumulation of CSCs failed to differentiate. When CSCs labeled by iron oxide, MRI showed that bFGF significantly enhanced the CSC engraftment compared with CSC transfer alone, contributing to cardiovascular regeneration detected by FISH analysis.
Conclusions: These results suggest that controlled release of bFGF may improve CSC survival and alter post-ischemic microenvironment to optimize CSC therapy in chronic myocardial infarction. This integrated biotherapy is safe and feasible, when appropriate number of CSCs was injected.