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Early-Onset Metformin Regimen Inhibits Radiation-Induced Fibrosis In Mice Model
Yusuf Surucu, MD; Katherine S. Yang, BS; Somaiah Chinnapaka, PhD; Alexey Altman; Michael W. Epperly, PhD; Joel S. Greenberger, MD; J. Peter Rubin, MD; Asim Ejaz, PhD
University of Pittsburgh
2023-02-10
Presenter: Yusuf Surucu
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting.
Director Name: J. Peter Rubin, MD, MBA
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Breast (Aesthetic and Recon.)
Introduction:
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. 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 for a month. The early cohort started the treatment immediately; the late cohort was delayed to 14th post-irradiation day to investigate the progression of limb movement and inhibition of fibrosis on day 35 and 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 in blind fashion.
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, metformin group failed to inhibit significant fibrosis. In contrast, the effect of cell therapies did not diminish to the level of insignificance.
Conclusions:
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.
