ABSTRACT
Three-dimensional in vitro skin models provide an alternative to animal testing for assessing tissue damage caused by chemical or physical agents and for the identification and characterization of agents formulated to mitigate this damage. The StrataTest® human skin model made with pathogen-free NIKS® keratinocyte progenitors is a fully-stratified tissue containing epidermal and dermal components that possesses barrier function as determined by measurements of electrical impedance. Independent batches of skin tissues responded consistently to known chemical irritants even after refrigerated storage for up to 7 days. Reactive oxygen species (ROS) were detected after exposure of skin tissues to ozone, cigarette smoke or ultraviolet (UV) irradiation. Pretreatment with the antioxidant parthenolide-depleted (PD)-Feverfew extract prevented cigarette smoke-induced or UV irradiation-mediated increases in ROS. Interleukin (IL)-1α and IL-1 receptor antagonist (IL-1RA) secretion increased in a dose dependent manner following UV irradiation but cytokine release was abrogated by pretreatment with a UVA/UVB sunscreen. Similarly, immunohistochemical detection showed increased thymidine dimer formation in UV-irradiated skin tissue that was prevented with sunscreen pretreatment. These results demonstrate that the StrataTest® human skin model is broadly applicable to a wide range of in vitro toxicological assays.
