Work

SP13. Early-Onset Metformin Regimen Inhibits Radiation-induced Fibrosis in Mice Model

Year: 2023

Type: article

Abstract: PURPOSE: Radiation-induced fibrosis (RIF) is a pathology characterized by large deposition of matrix and excessive proliferation of fibroblasts leading to reduced tissue function and quantity of life. Currently, very few safe and effective treatment options are available. Our goal was to test early and late regimens of a safe and well-tolerated FDA-approved agent (metformin) for RIF inhibition. METHODS: We used 40 Gy hind limb irradiated C57BL/6 mice as a skin fibrosis model and injected 100 mg/kg of metformin intraperitoneally twice a week. The early cohort started the treatment immediately; the late cohort was delayed to 14th post-irradiation day to investigate the inhibition of fibrosis on day 42. PBS-injected mice were used as a control group. Regimens were combined with either autologous or allogeneic adipose stem cells. The degree of limb excursion, epithelial thickness, and a histological fibrosis scale were employed. RESULTS: Allogenic and autologous cells successfully mitigated fibrosis; superior histological scoring and significantly improved limb excursion and epithelial thickness were achieved compared to the control. Earlier treatment increased the mitigation of fibrosis in all cohorts. The acute metformin treatment gave outcomes comparable to cell injections; when delayed, the metformin group failed to inhibit significant fibrosis. In contrast, the effect of cell therapies did not diminish to the level of insignificance. CONCLUSION: Our findings suggest that allogeneic stem cells and early-onset metformin treatment are possible promising therapeutic options to inhibit fibrosis. Further investigating regulatory markers in depth will be a step towards clinical adaptation as a RIF prophylaxis.

Source: Plastic & Reconstructive Surgery Global Open

DOI: 10.1097/01.gox.0000938396.18598.0d