Enhancement of long-term angiogenic efficacy of adipose stem cells by delivery of FGF2

Abstract

Stem cell transplantation can induce neovascularization. Regenerated blood vessels should remain stable for a long-term period in order to function as new blood vessels in ischemic tissues. Here we show that local delivery of FGF2 enhances the long-term (12 weeks) angiogenic efficacy of human adipose-derived stem cells (hADSCs) implanted into mouse ischemic hindlimbs. Following transplantation of hADSCs into ischemic hindlimbs of mice, hADSC viability was significantly higher in the hADSC + FGF2 group at 4 and 12 weeks post-transplantation than in the hADSC only group. Furthermore, hADSCs produced higher levels of angiogenic growth factors (i.e., fibroblast growth factor 2, vascular endothelial growth factor, hepatocyte growth factor, and platelet-derived growth factor) at both time points. As a result, the density of arterioles in the ischemic hindlimb muscle was significantly higher in the hADSC + FGF2 group than in either hADSC or FGF2 only group at both time points. The number of arterioles with larger diameters was significantly greater in the hADSC + FGF2 group than in the other groups at 12 weeks, and increased in the hADSC + FGF2 group as the time period increased from 4 weeks to 12 weeks post-transplantation. This suggests that FGF2 delivery to hADSC transplantation sites enhances long-term angiogenic efficacy of hADSCs transplanted into ischemic tissues.