IGF-I and Hyaluronic Acid Mitigate the Negative Effect of Irradiation on Human Skin Keratinocytes

SIMPLE SUMMARY: Patients undergoing radiation therapy for the treatment of various types of cancer often experience side effects such as radiation dermatitis. A gold standard treatment is still lacking. The objective of the present study was to find novel therapeutic strategies for the regeneration and repair of damaged skin areas after irradiation. An in vitro 2D and 3D primary keratinocyte model was used to test the effect of insulin-like growth factor I (IGF-I), keratinocyte growth factor (KGF), platelet lysate (PL), hyaluronic acid (HA), and adipose-derived stem cell (ADSC) conditioned medium on the functional abilities (viability, migration) and the gene expression of irradiated keratinocytes. Hyaluronic acid and IGF-I effectively reduced the irradiation damage of primary keratinocytes by stimulating viability and migration and reducing cell apoptosis and necrosis. These findings indicate that the negative effects of irradiation on keratinocytes located in the patient’s skin can be counterbalanced with HA and IGF-I treatment. ABSTRACT: Ionizing radiation has become an integral part of modern cancer therapy regimens. Various side effects, such as radiation dermatitis, affect patients in acute and chronic forms and decrease therapy compliance significantly. In this study, primary keratinocytes were irradiated in a 2-dimensional (2D) culture as well as on a 3-dimensional (3D) collagen-elastin matrix with doses of 2 and 5 Gy. The effect of different concentrations of IGF-I, KGF, platelet lysate (PL), high and low molecular weight hyaluronic acid (H-HA, L-HA), and adipose-derived stem cell (ADSC) conditioned medium was analyzed in respect to cell viability (WST-8), wound closure (migration), and the gene expression (quantitative real-time PCR) of 2D cultures. The 3D culture was evaluated by WST-8. A mixture of H-HA and L-HA, as well as IGF-I, could significantly stimulate the keratinocyte viability and migration which were severely reduced by irradiation. The MKI67and IL6 gene expression of irradiated keratinocytes was significantly higher after H-HA/L-HA treatment. The stimulating effects of H-HA/L-HA and IGF-I were able to be confirmed in 3D culture. A positive influence on cell viability, migration, and gene expression was achieved after the treatment with H-L-HA and IGF-I. These results open the possibility of a novel therapeutic method for both the prevention and the treatment of radiation dermatitis.