<< Back to the abstract archive
Evaluation of Metformin and Adipose-Derived Stem Cells Combination Therapy for Radiation Induced Fibrosis
Hamid Malekzadeh, Yusuf Surucu, Jose A. Arellano, Somaiah Chinnapaka, Michael W. Epperly, Joel S. Greenberger, J. Peter Rubin, Asim Ejaz
Department of Plastic Surgery, University of Pittsburgh Medical Center
2024-01-15
Presenter: Hamid Malekzadeh
Affidavit:
Certified
Director Name: J. Peter Rubin
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Introduction: Radiation-induced fibrosis (RIF) is a progressive pathology resulting in skin ulceration, dermal thickening, and the need for reconstructive surgery. Current management includes physical therapy, steroids, and fat grafting, but their efficacy is limited. This study explores the potential of metformin, autologous and allogeneic adipose stem cells (ASCs), and their combined therapy to enhance RIF treatment.
Methods: We used C57BL/6 mice irradiated with 40 Gy to establish a hind limb skin fibrosis model. We assessed metformin (100 mg/kg, intraperitoneal), ASCs, and their combination as mitigators. We tested both prophylactic (initiated post-irradiation on day 1) and therapeutic (starting on day 14) approaches. We assessed limb excursion, histology sections, and inflammatory and profibrotic genes expressions.
Results: after six weeks, metformin and ASCs demonstrated improved range of motion and histologic scores for inflammation and fibrosis (p<0.01). However, combining them did not show synergistic benefits in this context (p>0.05). In the therapeutic cohort, autologous ASCs, alone or with metformin, improved outcomes. Moreover, prophylactic treatment outperformed late-onset therapy in mitigating radiation-induced skin damage. Analyzing gene expression in transwell co-cultures revealed that ASCs and metformin, alone or combined, downregulated inflammatory and profibrotic gene expression in both mouse and human fibroblasts (p<0.001).
Conclusion: Our study highlights metformin's efficacy as a prophylactic measure against RISF. Furthermore, both autologous and allogeneic ASCs demonstrate substantial potential for prophylactic and therapeutic RIF treatment.
