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Fat Grafting Reduces Radiation-Induced Fibrosis in a Mouse Model

M. Asher Schusterman II, Asim Ejaz, Michael W. Epperly, Renee Fisher, X. Zhang, Moriah Johngrass, Lauren E. Kokai, Joel S. Greenberger, J. Peter Rubin.
UPMC
2018-02-12

Presenter: M. Asher Schusterman II

Affidavit:
This is the original work of the resident.

Director Name: Vu T. Nguyen

Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction

Background: Radiation therapy can result in the rare complication of radiation-induced fibrosis (RIF). This study assesses the ability of fat grafting to ameliorate RIF using an in vivo mouse model of hind limb fibrosis.

Methods: Female C57BL/6 mice were irradiated to the right flank to 35Gy in single fraction with 6Mv electron beam. The irradiated and contralateral non-irradiated limb tissue was monitored for expression of fibrosis related genes at days 1 and 14 post irradiation. Fibrosis was confirmed by histologic staining for collagen and range of limb motion measurements. Irradiated fibrotic sites were injected at day 28 with whole fat harvested from luciferase+ GFP+ mice.

Results: RIF was uniformly detected at day 14, amplified by day 28, and confirmed by histological staining for collagen by Masson's Trichrome. At day 14 there was upregulation of fibrosis-related genes: TGF-â (500 fold), CTGF (60 fold), Collagen 1 (400 fold), Collagen3 (500 fold) and collagen4 (500 fold) compared to non-irradiated contralateral hind limb tissue. Irradiation induced by day 28 showed a reduction in limb excursion with a range of limb extension of 11.4 ± 2.7 degrees compared to 57.0 ± 2.5 degrees (p < 0.0001) in the contralateral, non-irradiated limb. An injection of fat at day 28 significantly restored the limb excursion to 42.5 ± 2.5 degrees (p = 0.0013).

Conclusion: Our preliminary data supports clinical observations that fat grafting has benefit for treating RIF.

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