Culture of skin cells in 3D rather than 2D improves their ability to survive exposure to cytotoxic agents

In this study, we asked the question of whether cells in 3D culture cope more effectively with cytotoxic agents than cells in 2D. The sensitivities of human skin cells (keratinocytes, dermal fibroblasts and endothelial cells) to oxidative stress (hydrogen peroxide) and to a potentially toxic heavy metal (silver) when cultured under 2D and 3D conditions were investigated. The results show a marked resistance of cells to a given dose of hydrogen peroxide or silver nitrate causing a 50% loss of viability in 3D cultures, when compared to the same cells grown in 2D. There was also an improvement in the ability of cells to withstand both stresses when cells were in co-culture rather than in mono-culture. Foetal calf serum was found to have a mild protective effect in 2D culture but this was not extended to findings in 3D culture. This study suggests that dermatotoxicity testing using 3D co-cultures might be more likely to reflect true physiological responses to xenobiotic materials than existing models that rely on 2D mono-cultures.