1224 A Systematic Review Exploring the Mechanisms Behind Autologous Lipotransfer for Radiation-Induced Fibrosis

Abstract

Abstract Aim Radiation-induced fibrosis (RIF) is a recognised consequence of anti-cancer radiotherapy, especially after multiple and prolonged dosing regimens. There is no definitive treatment for late-stage RIF, although the use of autologous fat transfer (AFT) has shown promise. However, the exact mechanisms by which AFT improves RIF remain poorly understood. We aim to explore existing literature on the effects of AFT on both in-vitro and in-vivo RIF models, and to collate potential mechanisms of action. Method PubMed, Cochrane reviews and Scopus electronic databases from inception to January 2022 were searched. Our search strategy combined both free-text terms with Boolean operators, derived from synonyms of adipose tissue and RIF. Results The search strategy produced 2645 articles. Of these, 76 underwent full-text review for eligibility, yielding 26 for final analysis. Eight conducted in-vitro experiments utilising a co-culture model, whilst 21 conducted in-vivo experiments. AFT interventions included adipose-derived stem cells (ADSCs), stromal vascular function, whole fat and microfat. Notable findings include downregulation of fibroblast proliferation, collagen deposition, epithelial cell apoptosis, and proinflammatory processes. AFT suppressed hypoxia and pro-inflammatory interferon-γ signalling pathways, and ADSC-treated tissue stained strongly for anti-inflammatory M2 macrophages. Although largely proangiogenic initially, studies show varying effects on vascularisation. There is early evidence that ADSC subgroups may have different functional properties. Conclusions AFT 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 RIF. Further research should focus on ADSC sub-populations and augmentation techniques such as cell-assisted lipotransfer.