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Human Adipose-derived Stem Cells Decrease Skin Damage In Mice After Scalp Irradiation: A Pilot Experiment
Francisco R. Avila, MD, Ricardo A. Torres-Guzman, MD, Karla C. Maita, MD, John P. Garcia, MD, Abdullah S. Eldaly, MD, Luiza Palmieri-Serrano, BS, MS, Omar S. Emam, MD, Abba C. Zubair, MD, PhD, Alfredo Quinones-Hinojosa, MD, Antonio J. Forte, MD, PhD, Rachel Sarabia-Estrada, DVM, PhD.
Mayo Clinic Florida, Jacksonville, FL, USA.

PURPOSE: The treatment for radiation dermatitis ulcers is surgical reconstruction. We aimed to characterize the effects of human adipose-derived stem cells (hAdMSCs) to prevent complications of radiation dermatitis of the scalp in an immunocompetent mouse model.METHODS: Two 4-week-old female C57BL/6 mice were delivered a dose of 60 Gy to a skin area between the coronal and lambdoid sutures using a 5 mm circular collimator. On day 12 after irradiation, 600,000 luciferase- and green fluorescent protein-labeled hAdMSCs in 300 L of PBS were injected subcutaneously into the scalp of one mouse. Mice were photographed under standardized conditions and weighted daily. Bioluminescence imaging (BLI) was performed daily from the day after injection until there was no detectable signal. Both were euthanized on day 27 after irradiation, and the scalp tissue was collected. Staining with hematoxylin and eosin, Massons trichrome, and immunohistochemistry for CD31 were performed. The histological slides were digitalized and analyzed using ImageJ (NIH). Statistical analyses were performed using Excel 2010 (Microsoft Corp., United States).RESULTS: Bioluminescence images showed that hAdMSCs survived in vivo for five days (figure 1). While desquamation and ulceration appeared on day 14 and lasted for 12 days in the treated mouse, the control mouse did not show signs of improvement by the time of euthanasia (figure 2). The treated mouse had a greater mean erythematous area than the control mouse (0.38 cm2 vs. 0.23 cm2, p<0.05). The mean ulceration areas did not differ between the treated and control mouse (0.12 cm2 vs. 0.14 cm2, p>0.05). The epidermis, total skin thickness, and hypodermis of the irradiated regions were significantly thicker than the non-irradiated regions in both the treatment and control mice (figure 3). The vessel size (treated = 67.25 m2, control = 72.27 m2, p>0.05) and the difference in tissue area occupied by vessels (treated = 2.58%, control = 2.42%, p>0.05) of the radiated regions did not differ between mice. Collagen deposition in the irradiated region was decreased in the treated mouse compared to the control mouse (11% vs. 42%).CONCLUSION: Human adipose-derived stem cells decrease the duration of ulceration and improve the macroscopic quality of the skin, survive for only 5 days after transplantation, decrease collagen deposition in the irradiated area, increase micro vessel area and size, and decrease the thickness of the irradiated area of the skin compared to controls two weeks after transplantation.



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