Work

SP09. Allogeneic Adipose Tissue-derived Matrix Mitigate Radiation-induced Fibrosis

Year: 2023

Type: article

Abstract: PURPOSE: Radiation-induced fibrosis (RIF) is a complex tissue response characterized by massive deposition of extracellular matrix (ECM) and excessive fibroblast proliferation resulting in loss of tissue function and quality of life. This study tested the efficacy of an allograft adipose tissue-derived matrix (AATM) to mitigate RIF. METHODS: We used 40 Gy hind limb irradiated C57BL/6 mice as a skin fibrosis model and injected 200 μl AATM on the 14th post-irradiation day to investigate the inhibition of fibrosis on day 40. PBS and adipose stem cell (ASC) injections were negative and positive controls, respectively. The degree of limb excursion, skin epithelium thickness, and collagen deposition was measured as a marker of fibrosis. Molecular changes in treated and control skin were measured using real-time PCR and Luminex assay. In vitro, trans-well studies were performed to analyze the effect of direct coculture of irradiated cells with AATM on pro-fibrotic gene expressions. RESULTS: AATM treatment was as successful as ASC in diminishing fibrosis; decreased epithelial thickness, collagen deposition, and significantly improved limb excursion achieved compared to the negative control. In AATM-treated mice, real-time PCR analysis revealed the down-regulation of expression of pro-fibrotic genes TGF-β, CTGF, Col1, Col2, and TNF-alpha; similar down-regulation was observed in direct coculture studies in irradiated fibroblasts. CONCLUSION: Our findings suggest that allogeneic adipose tissue-derived matrix (AATM) can be an effective therapeutic option to mitigate fibrosis. Further studies to optimize the time and dose of the therapy will be a significant step toward clinical adaptation as a RIF treatment.

Source: Plastic & Reconstructive Surgery Global Open

DOI: 10.1097/01.gox.0000938380.41422.05