The Disturbed Function of Neutrophils at the Early Stage of Fat Grafting Impairs Long-Term Fat Graft Retention

BACKGROUND: Fat grafting is a popular soft-tissue filler method; however, the mechanism of its survival and regeneration is still not fully understood. Neutrophils are the frontier inflammatory cells and closely associated with tissue regeneration. To understand the role of neutrophils in fat graft retention, we adopted neutrophil depletion and up-regulation models. METHODS: Mouse inguinal fat (approximately 200 mg) was transferred autologously. The anti-mouse Ly6G antibody and lipopolysaccharides were used in the mouse fat grafting model for neutrophil depletion or activation, respectively. We examined the blood and graft stromal vascular fraction by fluorescence-activated cell sorting in manipulation/control groups. Graft weight, vascularization, and secreted factors were also compared. RESULTS: There was a significant reduction/increase of neutrophil counts in the circulation and the transferred fat before day 7 with Ly6G antibody/lipopolysaccharides treatment. Early depletion of neutrophils resulted in incompetent angiogenesis and eventually a poor retention rate (27 ± 8 percent) compared with control (51 ± 10 percent; p < 0.05), whereas up-regulated neutrophils increased the inflammation and reactive oxygen species level, leading to tissue damage and poor retention rate (20 ± 9 percent) compared with control (51 ± 10 percent; p < 0.05). Enhanced macrophage infiltration could be found in both neutrophil depletion and up-regulation groups after week 4. CONCLUSIONS: Undisturbed neutrophil function is the key to initiating downstream responses of macrophage infiltration, stimulating vessel formation, and regulating inflammation level; thus, it exerts a great impact on the long-term retention rate. Disturbed neutrophil function, either enhanced or weakened, can lead to impaired fat graft retention.