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Page 16 of 18 Rodriguez. Plast Aesthet Res 2023;10:67 https://dx.doi.org/10.20517/2347-9264.2023.73

SUMMARY
Plastic Surgeons have known for 2 decades that fat grafts reverse radiation damage. The effect has been
attributed to MSCs in the fat graft’s SVF. This article provides a broad overview of the molecular
mechanisms involved in the healing of irradiated tissue by MSCs.

Radiation damage itself can be understood as having an acute inflammatory phase (ARS) and a chronic
phase (RIF). Both phases are characterized by an organized tissue response that has its own set of alarm
signals, sentinel cells, signal amplification, immune effector cells, and target cells. In the case of RIF,
L-TGF-β (abundant in the matrix) acts as a redox sensor and releases TGF-β. TGF-β is known as the
“master regulator of fibrosis”. It precipitates a series of changes in cell behavior that culminate in
hypocellularity with a predominance of fibrocytes and myofibroblasts in a fibrotic matrix. HGF counteracts
the effects of TGF-β, and the interplay between the two cytokines has been referred to as the “Yin-Yang of
Fibrosis”. HGF is essential to all aspects of regeneration and triggers the “mitotic growth program” in
addition to having immune modulatory properties. The activity profile of HGF is strikingly like that of
MSCs. Investigators have used HGF gene promoters in MSCs that show HGF-enhanced MSCs demonstrate
significantly enhanced radioprotective effects compared to unaltered MSCs. In vitro experiments show that
knocking out the HGF gene in MSCs nullifies their radioprotection.

It is hoped that the insights gained from this review will propel new advances in regenerative fat grafting by
focusing on the role of the fat graft as a delivery vehicle for HGF.

DECLARATIONS
Authors’ contributions
The author contributed solely to the article.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
The author declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2023.

REFERENCES
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2. Rigotti G, Marchi A, Galiè M, et al. Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process
mediated by adipose-derived adult stem cells. Plast Reconstr Surg 2007;119:1409-22. DOI