Transplantation of cord blood-derived mesenchymal stem cells (CBMSCs) into ischemic regions could be a potential therapy for the treatment of ischemic disease, but its efficacy is limited by poor cell survival. We hypothesized that local delivery of fibroblast growth factor 2 (FGF2) to the site of CBMSC transplantation would enhance the viability of CBMSCs transplanted to ischemic tissues. Human CBMSCs were loaded onto fibrin gel with or without FGF2 and transplanted intramuscularly into either normal or ischemic hindlimbs of athymic mice. CBMSC transplantation combined with FGF2 delivery resulted in significantly lower apoptosis and higher survival of transplanted CBMSCs. The enhanced cell survival could be due to the local delivery of FGF2 and the enhanced secretion of anti-apoptotic factor. CBMSC transplantation and FGF2 delivery enhanced the expression of host-derived, platelet-derived growth factor-beta and NG2, which induce endothelial cell homing and pericyte recruitment, respectively, and more effectively protected muscles from ischemic degeneration when compared to CBMSC transplantation alone. FGF2 delivery to the site of CBMSC transplantation can enhance the survival of CBMSCs transplanted into ischemic tissues. This approach could be used to improve the angiogenic efficacy of CBMSC transplantation therapy for ischemic disease. (C) 2011, The Society for Biotechnology, Japan. All rights reserved.