Abstract
BackgroundRadiation-induced dermatitis is a serious side effect of radiotherapy, and very few effective treatments are currently available for this condition. We previously demonstrated that apoptosis is an important feature of radiation-induced dermatitis and adipose-derived stem cells (ADSCs) are one of the most promising types of stem cells that have a protective effect on acute radiation-induced dermatitis. Cathepsin F (CTSF) is a recently discovered protein that plays an important role in apoptosis. In this study, we investigated whether ADSCs affect chronic radiation-induced dermatitis, and the underlying mechanisms involved.MethodsADSCs were isolated from male Sprague-Dawley (SD) rats and characterized. For in vivo studies, rats were randomly divided into control and ADSC-treated groups, and cultured ADSCs were transplanted into radiation-induced dermatitis model rats. The effects of ADSC transplantation were determined by skin damage scoring, histopathological analysis, electron microscopy, immunohistochemical staining, and western blotting analysis of apoptosis-related proteins. To evaluate the effects of ADSCs in vitro, radiation-induced apoptotic cells were treated with ADSC culture supernatant, and apoptosis-related protein expression was investigated by TUNEL staining, flow cytometry, and western blotting.ResultsIn the in vivo studies, skin damage, inflammation, fibrosis, and apoptosis were reduced and hair follicle and sebaceous gland regeneration were enhanced in the ADSC group compared with the control group. Further, CTSF and downstream pro-apoptotic proteins (Bid, BAX, and caspase 9) were downregulated, while anti-apoptotic proteins (Bcl-2 and Bcl-XL) were upregulated. In vitro, ADSCs markedly attenuated radiation-induced apoptosis, downregulated CTSF and downstream pro-apoptotic proteins, and upregulated anti-apoptotic proteins.ConclusionADSCs protect against radiation-induced dermatitis by exerting an anti-apoptotic effect through inhibition of CTSF expression. ADSCs may be a good therapeutic candidate to prevent the development of radiation-induced dermatitis.
Highlights
Radiation-induced dermatitis is a serious side effect of radiotherapy, and very few effective treatments are currently available for this condition
Skin injury scores during the observation period are shown in Fig. 2B; the scores were lower in the adipose-derived stem cells (ADSCs) group than in the control group from 3 to 5 weeks post-irradiation (Fig. 2B, green dotted line)
In this study, we found that ADSCs decreased skin tissue damage, promoted hair follicle and sebaceous gland regeneration, and inhibited lymphocyte infiltration, apoptosis, and fibrosis formation, demonstrating that ADSCs alleviate acute and chronic radiation-induced dermatitis
Summary
Radiation-induced dermatitis is a serious side effect of radiotherapy, and very few effective treatments are currently available for this condition. Chronic radiation-induced dermatitis usually occurs more than 90 days after radiotherapy and is characterized by fibrosis and thickening of the dermis [3, 4]. Radiation-induced dermatitis may limit the radiation dose delivered and even necessitate treatment termination. This condition is treated using drugs, wound dressing, and even surgical treatment [1, 5]. These interventions have various limitations, such as poor efficacy or high risk; new effective treatments are urgently needed
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