Abstract
Cutaneous radiation syndrome (CRS) is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Here we examined for the first time in a large animal model the therapeutic potential of autologous adipose tissue-derived stroma cells (ASCs). For experiments, Göttingen minipigs were locally gamma irradiated using a 60Co source at the dose of 50 Gy and grafted (n = 5) or not (n = 8). ASCs were cultured in MEM-alpha with 10% fetal calf serum and basic fibroblast growth factor (2 ng.mL−1) and post irradiation were intradermally injected on days 25, 46, 67 and finally between days 95 and 115 (50×106 ASCs each time) into the exposed area. All controls exhibited a clinical evolution with final necrosis (day 91). In grafted pigs an ultimate wound healing was observed in four out of five grafted animals (day 130 +/− 28). Immunohistological analysis of cytokeratin expression showed a complete epidermis recovery. Grafted ASCs accumulated at the dermis/subcutis barrier in which they attracted numerous immune cells, and even an increased vasculature in one pig. Globally this study suggests that local injection of ASCs may represent a useful strategy to mitigate CRS.
Highlights
Skin is a radiosensitive tissue which is exposed to significant radiation doses in radiotherapy and radio-oncology as are the underlying muscles, nerves and vasculature structures [1]
Necropsy confirmed that the lesions were limited to the irradiated tissues behind the transversal epiphysis of the lumbar vertebrae: skin necrosis, thinning of the hypodermis (Fig. 3H), and hemorrhagic lesions or hyaline degeneration in the muscles were locally observed
We report the benefit of local autologous adipose tissue-derived stroma cells (ASCs) grafting to prevent/cure cutaneous radiation syndrome (CRS) in a large animal model close to human
Summary
Skin is a radiosensitive tissue which is exposed to significant radiation doses in radiotherapy and radio-oncology as are the underlying muscles, nerves and vasculature structures [1]. Intentional or accidental exposure of a relatively large area as well as localized ‘‘hot spot’’ exposures of the skin lead to severe damage of many of its cellular components and to the cutaneous radiation syndrome (CRS). The pathophysiology includes radiation-induced cell death (epidermal stem cell depletion, loss of capillary integrity) as well as impairment of the complex communication network between keratinocytes, dermal fibroblasts and resident or circulating immuno-competent cells. Irradiation severely impairs wound healing which normally requires a well-orchestrated integration of complex biological and molecular events, including cell migration and proliferation, extracellular matrix deposition, angiogenesis and remodelling. Nowadays the treatment schedules for severe radiation burns are complex, and include excision of the highly exposed necrotic areas Nowadays the treatment schedules for severe radiation burns are complex, and include excision of the highly exposed necrotic areas (likely .20 Gy) followed by transient coverage of the wound bed and by autologous skin grafts
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