N-Acetylcysteine (NAC) Improves Autologous Fat Graft Survival: A Preclinical Study

Purpose: Autologous fat grafting is an increasingly popular technique for soft tissue reconstruction, but is limited by inconsistent graft take, undercorrection, and repeat procedures. The authors examined whether a widely available, clinically safe anti-oxidant, N-acetylcysteine (NAC), could be added to tumescent solution at time of harvest to improve fat graft survival in a mouse model.

Methods: Inguinal fat grafts were harvested from C57BL/6 mice using tumescent solution with or without NAC, and injected under recipient mouse scalps. Fat graft volumes were evaluated via microCT and Materialise’s Interactive Medical Imaging Control System (MIMICS) volumetric analysis at 4 days (baseline), and 1 and 3 months post-injection. Explanted grafts were weighed and evaluated histologically for vascularity and quality. Flow cytometric analysis (FACS) and MTT assays were performed on adipose-derived stem cells (ADSCs) exposed to oxidative stress (hydrogen peroxide) with and without NAC.

Results: N-acetylcysteine resulted in improved fat graft retention, with 46% take in NAC animals, compared to 17% in controls (p=0.027). Explanted grafts from the NAC group were significantly larger (46 vs. 8 milligrams, p<0.01) and had a 133% higher mean adipocyte density (p<0.0001) than controls. No increase in vascularity was observed. FACS analysis demonstrated that NAC protected ADSCs from oxidative stress in a dose-dependent manner. Combined exposure to both NAC and hydrogen peroxide led to a 200-fold increase in ADSC proliferation, significantly higher than with either agent alone.

Conclusions: Addition of NAC to tumescent fluid for harvest of fat improves graft survival and quality in a mouse model. Our in vitro findings suggest that this effect is the result of protection from oxidative stress and increased survival of ADSCs and adipocytes.