Nutritional Regulation of Cultured Analogues of Human Skin

Abstract

Applications for a valid analogue of human skin include treatment of full-thickness skin wounds, alternatives to animals for safety testing of consumer products, and investigations of skin biology and pathology. In vitro models of cultured skin have been developed from combinations of cultured human keratinocytes and fibroblasts, and biopolymer substrates, but none has yet demonstrated regeneration of functional epidermal barrier. Formation of epidermal barrier in cultured skin depends greatly on the nutritional composition of incubation media to regulate proliferation and differentiation of keratinocytes into corneocytes and barrier lipids of stratum corneum. To simulate wound healing by keratinocytes, culture media should promote rapid proliferation early in the incubation period, followed by reduced proliferation and stimulation of synthesis of corneocytes and barrier lipids. Although functional epidermal barrier has not yet been produced in vitro, transplantation of cultured skin to animals and humans has demonstrated that true epidermal barrier can be generated by cultured epithelium. Understanding of the regulatory factors that promote stratum corneum formation has great potential for the generation of true epidermal barrier in vitro. Standardization and validation of analogues of human skin for therapeutic and diagnostic purposes will lead to meaningful advances in public health and safety.