Exosome-Mediated Enhancement of Fat Graft Retention: A Comparative Preclinical Study with Stromal Vascular Fraction

Background Cell-assisted lipotransfer (CAL) is a fat grafting technique that enhances graft survival by supplementing grafts with autologous stromal vascular fraction (SVF) or adipose-derived stromal cells (ASCs). However, its clinical translation has been hindered owing to inherent biological variability, potential cell viability issues, tumorigenic risk, and the complex regulatory landscape associated with cell-based therapies. To overcome these challenges, exosome has gained increasing attention as a promising non-cellular therapeutic modality capable of preserving key regenerative functions while minimizing relative concerns. This study aimed to compare the efficacy of SVF-enriched lipotransfer with fat co-transplanted with exosomes from ASCs to identify a reliable and clinically applicable non-cellular strategy for optimizing fat graft outcomes. Methods In vivo, minced human fat tissue mixed with phosphate-buffered saline, SVF cells, or exosomes was grafted into nude mice. Grafts were evaluated through microcomputed tomography at weeks 4 and 8 post-grafting and histological analysis at weeks 1 and 8 post-grafting. Results The exosome group showed a significantly higher volume retention rate than the control group at weeks 4 and 8 post-grafting. Histological analysis revealed that exosomes exhibited more pronounced effects in reducing inflammation, preserving perilipin-positive adipocytes, and promoting angiogenesis in the grafted fats compared with those of SVF cells. Conclusions Our findings highlight the potential of exosomes in improving fat graft retention and overall tissue regeneration, suggesting that fat co-transplanted with exosomes from ASCs could serve as a superior alternative to SVF-enriched lipotransfer. No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266