Indomethacin enhances fat graft retention by up-regulating adipogenic genes and reducing inflammation

Background: Cell-assisted lipotransfer has been promisingly applied to restore soft-tissue defects in plastic surgery; however, the harvesting of stromal vascular fraction increases morbidity and poses potential safety hazards. The authors investigated whether adding indomethacin, an antiinflammatory proadipogenic drug, to the fat graft at the time of transplantation would enhance the final graft volume compared with cell-assisted lipotransfer. Methods: In vitro, human adipose-derived stem cells were cultured in conditioned growth media supplemented with various doses of indomethacin to investigate adipogenesis and the expression of the adipogenic genes. In vivo, lipoaspirate mixed with stromal vascular fractions or indomethacin was injected into the dorsum of mice. Tissues were harvested at weeks 2, 4, and 12 to evaluate histologic changes. Results: In vitro, polymerase chain reaction analysis revealed that increased up-regulation of adipogenic genes and activation of the peroxisome proliferator-activated receptor-[gamma] pathway. In vivo, the percentage volume of adipocytes in the indomethacin-assisted groups was higher than that in the lipoaspirate-alone (control) group at 12 weeks (p = 0.016), and was equivalent to the volume in the cell-assisted groups (p = 1.000). Indomethacin improved adipose volumes but had no effect on vascularity. A larger number of small adipocytes appeared in the treatment samples than in the controls at 2 weeks (p = 0.044) and 4 weeks (p = 0.021). Conclusions: Pretreating lipoaspirate with indomethacin enhances the final volume retention of engrafted fat. This result is explained in part by increased adipogenesis and possibly by the inhibition of inflammatory responses.