Radiation dermatitis (RD) is a side effect of ionizing radiation delivered to the skin during cancer treatment. Furthermore, 95% of patients exposed to radiotherapy present skin reactions such as erythema, dry and moist desquamation and ulcerations. Because of these, sometimes it is necessary to stop the treatment until the skin is completely healed. The current treatment strategies are mid-potency topical corticosteroids combined with topical or systemic antibiotics if needed. According to the grading of injury, patients could need systemic treatment with steroids or biological agents and/or surgical debridement of wounds. These treatments exhibit some limitations, including local treatment failure, extended healing time and drug side effects. For those reasons, we propose a novel regenerative therapy that takes advantage of the paracrine effect of human adipose derived tissue mesenchymal stem cells (hAdMSCs) to recover a 2D <i>in vitro</i> keratinocytes radiodermatitis model. First, we established a radiodermatitis model using a 2D monolayer of HaCaT cells (CVCL_0038) exposed to a dose of 0.5, 1 and 2 Gy daily for 25 days, according to breast cancer regimen. Parallelly, the hAdMSCs were cultured to obtain the conditioned medium (CM) with the potentially regenerative metabolites and then the model was exposed to different concentrations of CM. We evaluated cell viability, proliferation and recovery rate via commercially available kits and microscopic observation. Preliminary results show detrimental effects of radiotherapy in cell viability evaluated daily by LDH assay and consequently, we optimized the radiation dose. Additionally, the CM was evaluated via total protein contents with BCA assay and through an SDS-PAGE analysis to estimate possible major protein components. Future work will be focused on developing a 3D bioprinted radiodermatitis model based on hydrogels of extracellular matrix combined with keratinocytes and fibroblasts spheroids. Furthermore, we will continue with a more throughout characterization of CM by proteomic tools.

Paracrine effect of mesenchymal stem cells in an <i>in vitro</i> model of radiation-induced dermatitis

ACS Fall 2021

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Paracrine effect of mesenchymal stem cells in an in vitro model of radiation-induced dermatitis