Alpha-1-Antitrypsin Enhances Fat Graft Survival in a Murine Model.

Abstract

OBJECTIVE: Fat grafting is widely applied for various purposes, including volume restoration, improving tissue quality, and promoting wound healing, but it has poor long-term graft survival predictability. Alpha-1-antitrypsin (AAT) administration is hypothesized to improve fat graft outcomes by expediting inflammatory resolution and graft vascularity and reducing necrosis. APPROACH: Mice heterozygote to human AAT was grafted fat under the scalp alongside 400 µg/graft AAT or albumin (ALB) on days 0 and 3. Graft volume was determined by micro-magnetic resonance imaging, and explants were assessed for viability, histology, immunohistochemistry, and expression of selected genes. AAT expression was examined in hypoxia-exposed adipose-derived stem cells (ADSCs). RESULTS: After 90 days, AAT-treated grafts maintained higher volumes (70.06% vs. 34.54%,= 8,= 0.02) and displayed improved tissue quality. On day 10 after grafting, grafts exhibited more blood vessels (mean 1.94/mmvs. 0.33/mm) and 6.25-fold more adiponectin transcript levels (= 12,= 0.02). Although day-3 interleukin (IL)-1β expression was 5-fold greater in AAT-treated grafts (= 6,= 0.4), day-10 IL-1β expression was 2-fold lower compared to ALB-treated grafts (= 22,= 0.01). In the Methoxynitrosulfophenyl-tetrazolium carboxanilide (XTT) assay, day-3 AAT-treated grafts were 1.56-fold more metabolically functional (= 6,= 0.04) and exhibited greater perilipin-positive regions (18.5% versus 3.1%). Hypoxia-exposed ADSC expressed 9-fold higher AAT transcript levels (= 0.04). INNOVATION: Fat grafting outcomes improved by early AAT treatment, probably by accelerating inflammatory resolution. Due to its marked safety profile, the study's findings are for adjunct clinical-grade AAT therapy. CONCLUSION: AAT has a promising potential to be utilized as a fat graft outcome enhancer in terms of volume retention predictability and tissue quality.[Figure: see text].