Enhanced Effect of Secondary Administration of Adipose-Derived Stromal Cells Concurrent with Fat Grafting

BACKGROUND: Cell-assisted lipotransfer, a fat graft mixed with adipose-derived stromal cells, is known to enhance fat graft retention. Previously, the authors showed that intravenous injection of adipose-derived stromal cells can improve the survival of grafted fat. In the present study, the authors investigated the effects of a secondary intravenous injection of adipose-derived stromal cells on fat grafting. METHODS: Wild-type C57BL/6J (B6) mice were used as donors for grafted fat and as recipients. Adipose-derived stromal cells were harvested from green fluorescent protein and DsRed B6 mice. The recipient mice were divided into three groups: SI ( n = 10), RI1 ( n = 10), and RI2 ( n = 11). All groups received intravenous injections of green fluorescent protein adipose-derived stromal cells immediately after fat grafting. The RI1 and RI2 groups received repeated intravenous injections of DsRed adipose-derived stromal cells at 1 and 2 weeks, respectively, after fat grafting. The grafted fat volume was measured using micro-computed tomography. RESULTS: Secondarily injected DsRed adipose-derived stromal cells were recruited to the grafted fat and resulted in a higher retention of graft volume and vascular density ( P < 0.05). The stromal-derived factor-1 and C-X-C chemokine receptor type 4 genes related to stem cell homing were highly expressed in the grafted fat and adipose-derived stromal cells ( P < 0.05). The RI2 group showed a higher graft volume and vascular density than the SI and RI1 groups ( P < 0.05). CONCLUSIONS: A secondary intravenous injection of adipose-derived stromal cells at a 2-week interval enhances the effect of adipose-derived stromal cell enrichment in fat grafting. These findings refine clinical protocols and enhance the therapeutic value of cell-assisted lipotransfer. CLINICAL RELEVANCE STATEMENT: In a modified animal model of cell-assisted lipotransfer, the authors demonstrated that secondary intravenous administration of adipose-derived stromal cells improved retention of grafted fat.