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

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.

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).

After 90 days, AAT-treated grafts maintained higher volumes (70.06% vs. 34.54%, n = 8, p = 0.02) and displayed improved tissue quality. On day 10 after grafting, grafts exhibited more blood vessels (mean 1.94/mm² vs. 0.33/mm²) and 6.25-fold more adiponectin transcript levels (n = 12, p = 0.02). Although day-3 interleukin (IL)-1β expression was 5-fold greater in AAT-treated grafts (n = 6, p = 0.4), day-10 IL-1β expression was 2-fold lower compared to ALB-treated grafts (n = 22, p = 0.01). In the Methoxynitrosulfophenyl-tetrazolium carboxanilide (XTT) assay, day-3 AAT-treated grafts were 1.56-fold more metabolically functional (n = 6, p = 0.04) and exhibited greater perilipin-positive regions (18.5% versus 3.1%). Hypoxia-exposed ADSC expressed 9-fold higher AAT transcript levels (p = 0.04).

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.

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].