The Chemokine Stromal Cell-Derived Factor-1α Promotes Endothelial Progenitor Cell-Mediated Neovascularization of Human Transplanted Fat Tissue in Diabetic Immunocompromised Mice

Background: Stromal cell-derived factor-1 alpha is a chemokine and mediates endothelial progenitor cell-induced neovascularization. Because vascularization of a graft is crucial for its survival, the authors investigated whether stromal cell-derived factor-1 alpha could improve fat graft survival by inducing endothelial progenitor cell-mediated neovascularization and preventing its resorption. Methods: The authors injected 1 ml of human fat tissue into the scalps of 30 diabetic and 10 nondiabetic immunocompromised mice. The fat grafts were treated with phosphate-buffered saline or stromal cell-derived factor-1 alpha. Determination of graft phenotype included measurements of their weights and volumes, vascular endothelial growth factor (VEGF) levels, the stromal cell-derived factor-1 alpha receptor CXCR4, VEGF receptor 2, endothelial nitric oxide synthase, serine/threonine-specific protein kinase (protein kinase B), caspase 3, and cytochrome c expression levels, and the extent of vascularization. Results: Eighteen days after transplantation, stromal cell-derived factor-1 alpha treatment of the grafts in the diabetic mice (1) increased plasma VEGF levels; (2) raised VEGF receptor 2, CXCR4, endothelial nitric oxide synthase, and protein kinase B expression levels; and (3) reduced caspase 3 and cytochrome c expression levels in the fat grafts. Fifteen weeks after transplantation, stromal cell-derived factor-1 alpha treatment of the grafts prevented their resorption and increased the extent of their vascularization. Conclusion: Locally delivered stromal cell-derived factor-1 alpha increases fat graft survival by stimulating neovascularization and reducing fat cell apoptosis through an endothelial progenitor cell-mediated mechanism.