Exploring the mechanisms behind autologous lipotransfer for radiation-induced fibrosis: A systematic review.

Aim: Radiation-induced fibrosis is a recognised consequence of radiotherapy, especially after multiple and prolonged dosing regimens. There is no definitive treatment for late-stage radiation-induced fibrosis, although the use of autologous fat transfer has shown promise. However, the exact mechanisms by which this improves radiation-induced fibrosis remain poorly understood. We aim to explore existing literature on the effects of autologous fat transfer on both in-vitro and in-vivo radiation-induced fibrosis models, and to collate potential mechanisms of action.

Method: PubMed, Cochrane reviews and Scopus electronic databases from inception to May 2023 were searched. Our search strategy combined both free-text terms with Boolean operators, derived from synonyms of adipose tissue and radiation-induced fibrosis.

Results: The search strategy produced 2909 articles. Of these, 90 underwent full-text review for eligibility, yielding 31 for final analysis. Nine conducted in-vitro experiments utilising a co-culture model, whilst 25 conducted in-vivo experiments. Interventions under autologous fat transfer included adipose-derived stem cells, stromal vascular function, whole fat and microfat. Notable findings include downregulation of fibroblast proliferation, collagen deposition, epithelial cell apoptosis, and proinflammatory processes. Autologous fat transfer suppressed hypoxia and pro-inflammatory interferon-γ signalling pathways, and tissue treated with adipose-derived stem cells stained strongly for anti-inflammatory M2 macrophages. Although largely proangiogenic initially, studies show varying effects on vascularisation. There is early evidence that adipose-derived stem cell subgroups may have different functional properties.

Conclusion: Autologous fat transfer functions through pro-angiogenic, anti-fibrotic, immunomodulatory, and extracellular matrix remodelling properties. By characterising these mechanisms, relevant drug targets can be identified and used to further improve clinical outcomes in radiation-induced fibrosis. Further research should focus on adipose-derived stem cell sub-populations and augmentation techniques such as cell-assisted lipotransfer.