Advancing fat graft survival: from adipose-derived stem cell mechanisms to next-generation regenerative strategies

Autologous fat grafting is widely used in reconstructive and aesthetic surgery because it is easy to harvest, well tolerated by the host, and produces natural-looking results. However, unpredictable graft resorption-with reported volume retention ranging from 30% to 80%-remains a major obstacle. To overcome this, two cell-based approaches have been developed: the stromal vascular fraction (SVF), a freshly isolated mixture containing approximately 1%-10% adipose-derived stem/stromal cells (ADSCs) plus other cell types, and culture-expanded ADSCs, a more homogeneous population obtained under Good Manufacturing Practice conditions. Meta-analyses show that while SVF increases fat retention by a modest margin, expanded ADSCs can achieve substantially greater improvements, highlighting important biological and regulatory differences between the two preparations. ADSCs support graft survival not only through classic growth factor secretion but also via immunomodulation, intercellular mitochondrial transfer, and exosomal microRNAs that co-ordinate angiogenesis, inflammation, and fibrosis. This review summarises current clinical evidence for ADSC- and SVF-enriched fat grafting in breast reconstruction, facial rejuvenation, scar management, chronic wounds, hair restoration, and paediatric as well as elderly populations. We also critically assess adjunctive strategies, including platelet-rich plasma, exosome-based acellular therapies, decellularized adipose matrices, engineered hydrogels, and nanofat grafting, and discuss the role of mitochondrial transfer enhancement. Standardised summary tables of clinical studies and emerging technologies are provided to facilitate evidence synthesis. Persistent challenges-such as the frequent conflation of SVF with ADSCs in the literature, the lack of standardised preparation and potency assays, and unresolved long-term oncological safety concerns-are examined, and priority areas for future research are proposed.