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Allogeneic Adipose Tissue-Derived Matrix Mitigate Radiation-Induced Fibrosis (RIF)
Surucu Y; Chinnapaka S; Katherine Y; Epperly M; Greenberger J; Rubin P; Ejaz A
University of Pittsburgh, Department of Plastic Surgery, Adipose Tissue Stem Cell Center
2022-01-19
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: General Reconstruction
Introduction: 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 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) injection 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 towards clinical adaptation as a RIF treatment.
