"Creating a Favorable Micro-Environment for Fat Grafting in a Novel Model of Radiation Induced Mammary Fat Pad Fibrosis."

• Published in: Plastic and reconstructive surgery (1963)
• Main Authors: Truong, Jessica L, Liu, Muhan, Tolg, Cornelia, Barr, Meredith, Dai, Cecilia, Raissi, Thomas C, Wong, Eugene, DeLyzer, Tanya, Yazdani, Arjang, Turley, Eva A
• Format: Journal Article
• Language: English
• Published: United States 30.09.2019
• ISSN: 1529-4242
• DOI: 10.1097/PRS.0000000000006344

Radio-fibrosis of breast tissue compromises breast reconstruction by interfering with tissue viability and healing. Autologous fat transfer may reduce radiotherapy-related tissue injury but graft survival is compromised by the fibrotic microenvironment. Elevated expression of Receptor for Hyaluronan-mediated motility (HMMR/RHAMM) in wounds decreases adipogenesis and increases fibrosis. We therefore developed RHAMM peptide mimetics to block RHAMM pro-fibrotic signaling following radiation. We propose that this blocking peptide will decrease radio-fibrosis and establish a microenvironment favoring adipose-derived stem cell survival using a rat mammary fat pad model. Rats mammary fat pads underwent a one-time radiation dose of 26 Gy. Radiated (n=10) and non-radiated (n=10) fat pads received a single intra-mammary injection of a sham injection or peptide NP-110. Skin changes were examined clinically. Mammary fat pad tissue was processed for fibrotic and adipogenic markers using QPCR and immunohistochemistry. Clinical assessments and molecular analysis confirmed radiation-induced acute skin changes and radiation-induced fibrosis in rat mammary fat pads. Peptide treatment reduced fibrosis as detected by polarized microscopy of picrosirius red staining, increased collagen 3:1 ratio, reduced expression of collagen-1 crosslinking enzymes lysyl-oxidase, transglutaminase 2 and TGFβ1 protein m and increased adiponectin, an anti-fibrotic adipokine. RHAMM was expressed in stromal cell subsets and was down-regulated by the RHAMM peptide mimetic. Results from this study predict that blocking RHAMM function in stromal cell subsets can provide a post-radiotherapy micro-environment more suitable for fat grafting and breast reconstruction.