Lipoaspirate:  Its Potential to Repair Radiation Damage in a Murine Model
Vishal D. Thanik, Oren Lerman,  Jamie P. Levine,  Pierre B. Saadeh, Sydney R. Coleman, Alexes Hazen
Institute of Reconstructive Plastic Surgery, New York University School of Medicine
Introduction
Anecdotal clinical reports suggest that subcutaneous fat grafting can ameliorate radiation skin damage. ^{1, 2} Adipose derived progenitor cells may play a role in this process.  In order to study this phenomenon, we have developed a novel mouse model of radiation-induced skin injury and used small volume, multiple-pass fat transfer to deliver processed lipoaspirate beneath the irradiated skin.
Methods
The dorsal skin of adult wild-type FVB mice was isolated with a low-pressure, non-ischemic clamp and exposed to a single dose of 45Gy XRT (dose determined through preliminary experiments).  Skin changes were assessed by gross examination, H&E, and immunohistologic evaluation every other week for up to 6 weeks after irradiation.  Human lipoaspirate was harvested from healthy female donors and processed by centrifuging for five minutes at 3000 rpm, and discarding the serous bottom layer and oil upper layer. Refined fat was transferred (1cc syringes) for immediate transplantation. Six weeks after XRT, mice with visible partial thickness radiation ulcers were infiltrated subdermally with 1.5mL of human fat using an 18-gauge Coleman cannula, utilizing a fan-like pattern over the mouse dorsum, 0.033mL fat injected per pass.  Controls received blind passes in a similar fashion.
Results
All mice tolerated irradiation well. Visible erythema, dermal thickening and skin changes were observed at each post-irradiation time point.  Sirius red staining of skin biopsies demonstrated increased collagen and fibrosis of the dermal layer.  This correlated with doppler analysis, which demonstrated  decreased dorsal skin perfusion.  Whole mount analysis of the dorsal skin after fat injection demonstrated viable injected fat with vascular infiltration.  Cytochrome c oxidase IV staining, which stains specifically for human tissue, demonstrated positive endothelial cell staining, indicating vascularity was human-derived. Histological analysis demonstrated vascularized viable human adipose tissue with nominal peripheral fat necrosis and fibroblastic infiltration.  Fat grafting resulted in rapid improvement in XRT skin changes compared to controls (Figure 1).
Discussion
This novel murine model of radiation injury is the first model that has been able to limit injury to the skin and reveals consistent, nonlethal dermal changes similar to human injury.  We have demonstrated that injected lipoaspirate survives and vascularizes in this murine model, and that the neo-vessels in the grafted fat are human derived, suggesting that the adipose derived stem cells know to reside in the fat are active.^3-5  Furthermore, subdermal fat grafting improved overlying irradiated skin quality and aided in ulcer repair. 
 

 Figure 1:
 

References

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