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Rodriguez. Plast Aesthet Res 2023;10:67 Plastic and
DOI: 10.20517/2347-9264.2023.73
Aesthetic Research

Review Open Access

Understanding how MSCs reverse radiation-induced
fibrosis: HGF vs. TGF-B1

Ricardo Luis Rodriguez

Department of plastic surgery, Cosmeticsurg, Lutherville, MD 21093, USA.
Correspondence to: Dr. Ricardo Luis Rodriguez, Department of plastic surgery, Cosmeticsurg, 1300 Bellona Ave., Suite C,
Lutherville, MD 21093, USA. E-mail: dr.rodriguez@me.com

How to cite this article: Rodriguez RL. Understanding how MSCs reverse radiation-induced fibrosis: HGF vs. TGF-B1. Plast Aesthet
Res 2023;10:67. https://dx.doi.org/10.20517/2347-9264.2023.73

Received: 28 Jul 2023 First Decision: 26 Sep 2023 Revised: 6 Nov 2023 Accepted: 17 Nov 2023 Published: 4 Dec 2023

Academic Editors: Joseph M. Rosen, Roberto Cuomo Copy Editor: Yanbing Bai Production Editor: Yanbing Bai

Abstract
Radiation induced fibrosis (RIF) can be understood as a form of chronic radiation-induced bystander effect (RIBE).
It is a fibrotic process different than acute radiation syndrome (ARS), which is an inflammatory process that has
different mediators and effector cells. It is triggered by Reactive Oxygen Species (ROS) activation of the matrix-
embedded L-TGF-β complex. TGF-β acts by directing cellular processes that culminate in a fibrotic state. These
include epithelial and endothelial mesenchymal transition (EMT and EnMT), G1 phase growth arrest, stimulation of
fibrosis, and apoptosis, characterized by hypocellularity with a predominance of fibrocytes and myofibroblasts,
fibrosis, and variable loss of tissue function. Fat grafting is the only clinically available tool to reverse RIF. The
reversal of RIF is mediated by the mesenchymal stem cells (MSCs) embedded in the stromal vascular fraction
(SVF) adipose tissue. The mechanism of action is the release of HGF (hepatocyte growth factor) by the MSCs into
the surrounding RIF tissue. The HGF initiates a “mitotic growth program” that reprograms cell behavior. These
changes include EMT and EnMT, stimulation of cell proliferation and morphogenesis, anti-apoptosis,
downregulation of TGF-β, dissolution of fibrosis, and cell motility. The “mitotic growth program” culminates in
tissue regeneration and reversal of RIF.

Keywords: HGF, TGF-β, RIF, radiation-induced fibrosis, fat grafting, MSC

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
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