Background: Fat grafting is widely utilized in plastic surgery; however, inconsistent graft retention remains a key clinical issue. One major limitation is the poor ischemic tolerance of transplanted adipose tissue, aiming to timely improving the vascularity of the grafted fat. Among various modified fat preparations, the mechanically processed tissue stromal vascular fraction (tSVF) has gained interest for its potential to improve fat graft survival. Further augmentation of graft quality and retention through supplements to tSVF is an area worth exploring.

Methods: An established rat arteriovenous (AV) shunt model was employed to assess the regenerative efficacy of glycolipid Globo H Ceramide (GHCer) added to tSVF obtained from male Lewis rats. The rats were randomly assigned to four groups. Outcome measures included gene expression of vascular endothelial growth factor A (VEGFA) and fatty acid binding protein 4 (FABP4), percentages of CD45^-CD31⁺ endothelial cells, fat graft retention, and degress of fibrosis. Complementary in vitro experiments with adipose-derived mesenchymal stromal cells (AD-MSCs) evaluated GHCer’s effects on angiogenesis via tube formation and on adipogenic differentiation.

Results: Grafts supplemented with GHCer showed significantly improved volume retention at 1, 2, and 8 weeks post-transplantation (p < 0.05). VEGFA expression was upregulated at week 1 (p < 0.05), followed by increased FABP4 expression at week 2 (p < 0.01) in the tSVF+GHCer group. By week 8, these grafts exhibited higher numbers of CD45^-CD31⁺ endothelial cells and adipocytes (p < 0.01) along with decreased collagen deposition (p < 0.05). In vitro, GHCer enhanced AD-MSC differentiation into both vascular structures (p < 0.05) and adipocytes (p < 0.001), suggesting a mechanistic link between GHCer’s effects and the MSC component within tSVF.

Conclusion: GHCer supplementation to tSVF significantly improved fat graft retention and reduced fibrosis while promoting angiogenesis and adipogenesis, likely by facilitating AD-MSC differentiation. These findings highlight the promise of GHCer as a therapeutic additive to enhance the long-term success of fat grafting procedures.