Adipose-Derived Stem Cell, Stromal Vascular Fraction, and Regenerative Cell Enrichment in Fat Grafting: A Systematic Review of Safety and Functional Outcomes

Adipose-derived stem cell (ADSC)-enhanced fat grafting, including enrichment with stromal vascular fraction (SVF) and adipose-derived regenerative cells (ADRCs), has been increasingly used to improve fat graft survival and regenerative outcomes in reconstructive and aesthetic plastic surgery, yet long-term safety, efficacy, and mechanistic understanding remain variably reported. This systematic review aimed to evaluate real-world clinical evidence on the long-term safety, volume retention, and functional outcomes of ADSC-, SVF-, and ADRC-enriched fat grafting across aesthetic and reconstructive indications. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, comprehensive searches of PubMed, Scopus, Web of Science, and the Cochrane Library identified 3158 studies, of which 12 met the inclusion criteria, encompassing randomized controlled trials and prospective non-randomized clinical studies assessing ADSC-, SVF-, or ADRC-assisted fat grafting with reported outcomes related to graft survival, clinical function, aesthetic performance, or safety. Across studies, ADSC and SVF enrichment generally improved volume retention compared with conventional fat grafting, with several randomized trials demonstrating graft survival rates of 60-80% at three to six months, and ADSC-assisted grafts consistently enhanced dermal regeneration by improving collagen organization, skin texture, and elastic fiber architecture. In reconstructive applications, SVF therapy reduced digital ulcers and pain in patients with systemic sclerosis, while ADRC-assisted grafting alleviated symptoms of breast cancer-related lymphedema despite limited objective limb-volume reduction, and patient satisfaction was high across all enrichment techniques. Safety outcomes were favorable, with no increase in infection, cyst formation, fat necrosis, or oncologic recurrence across follow-up periods of up to four years. Overall, ADSC-, SVF-, and ADRC-enriched fat grafting appear to offer meaningful improvements in graft survival, skin quality, and functional recovery with a strong safety profile across diverse clinical indications, although methodological heterogeneity and limited long-term data support the need for standardized, regulated, and mechanistically informed clinical protocols, as well as larger, long-term randomized trials to optimize techniques and guide clinical use.