CXCL12+ Adipose Stem Cells Enhance Fat Graft Vascularization by Recruiting Endothelial Progenitors

Autologous fat grafting is limited by unpredictable graft resorption, and early neovascularization is a critical determinant of graft survival. This study investigated whether co-transplantation of adipose-derived stem cells (ADSCs) overexpressing CXCL12 creates a chemotactic microenvironment that recruits endothelial progenitor cells (EPCs) and thereby promotes neovascularization. Human ADSCs were transduced to overexpress CXCL12. Fat grafts were mixed with CXCL12-overexpressing ADSCs (Group A), empty-vector-transduced ADSCs (Group B), unmodified ADSCs (Group C), or culture medium (Group D) and injected subcutaneously into nude mice. Circulating EPC counts and capillary density were assessed at multiple early time-points, and graft volume and histology on day 90. Group A showed sustained higher local SDF-1α levels, with concomitant increases in circulating EPC counts and consistently higher capillary density at all early time-points compared with controls. On day 90, graft survival rates in Groups A–D were 71.8 ± 1.7%, 55.8 ± 1.5%, 56.1 ± 0.8%, and 35.3 ± 2.1%, respectively (P < 0.001). Group A grafts displayed well-formed adipose lobules, preserved interlobular septa, and reduced fat necrosis and fibrosis (P < 0.01). Collectively, local SDF-1α overexpression by engineered ADSCs recruited circulating EPCs; the recruited EPCs, together with co-transplanted ADSCs, promoted neovascularization and improved long-term graft retention and histological quality.