Differentiation of bone marrow-derived mesenchymal stem cells into multi-layered epidermis-like cells in 3D organotypic coculture.

The interactions of bone marrow-derived mesenchymal stem cells (MSCs) and their engrafted microenvironment are an integral part of signaling control of stem cell lineage commitment. We attempted to induce bone marrow-derived MSCs to undergo epidermal lineage differentiation by manipulating the biochemical, environmental and physical properties of culture conditions in an organotypic coculture model to simulate a skin-specific microenvironment. The induction medium was optimized by varying different biomolecular supplements in a basic stratification medium. A multi-layered epidermis-like structure was established when MSCs were cultured in an optimized induction medium on a contractible fibroblast-embedded collagen gel with an air-liquid interface. The commitment into epidermal lineage was further confirmed by the expression of early and intermediate epidermalization markers - keratin 10 and filaggrin in 90.67% and 80.51% of MSCs, respectively. This study not only highlights the possibility of in vitro control of MSCs into epidermal lineage, but also suggests the therapeutic potential of bone marrow-derived MSCs for skin regeneration.