Abstract
Autologous stratified squamous epithelial cell sheets have been successfully used to treat epithelial defects in tissues such as the cornea and the esophagus. However, the regenerative cellular events occurring in the grafted epithelial cells are unclear in the early stages of wound healing. In this study, we created an in vitro grafting model using cultured normal human epidermal keratinocyte (NHEK) sheets and a type I collagen gel to investigate the cellular processes that occur within the grafted cell sheet. Cultured NHEK cells successfully became a stratified squamous cell sheet resembling epithelial tissue, retained expression of cellular integrins and adhesion proteins, and adhered successfully to a type I collagen gel. After culture on the collagen gel, expression of E‐cadherin, and β‐catenin decreased in the cells of the basal layer of the grafted cell sheet, resembling events characteristic of a partial epithelial–mesenchymal transition (EMT). These basal cells also induced migration of the cell sheet. Those phenomena are consistent with the essential events that occur in the wound‐healing process observed previously in cell studies. Therefore, the epithelial cell sheet grafted onto a type I collagen gel is a suitable model in vitro to study cellular events and behaviors. Furthermore, we also addressed the therapeutic mechanisms by which the epithelial cell sheet promotes wound healing.
Highlights
Autologous stratified squamous epithelial cell sheets have been successfully used to treat epithelial defects in tissues such as the cornea and the esophagus
We focused on the partial epithelial–mesenchymal transition (EMT) events in each layer, and examined the spatiotemporal expression of marker proteins that are indicative of epithelial-specific cell–cell adhesion (e.g., E-cadherin) as well as mesenchymal markers
Detached normal human epidermal keratinocyte (NHEK) cell sheets with a roughly circular shape were examined by IHC (Fig. 2)
Summary
Autologous stratified squamous epithelial cell sheets have been successfully used to treat epithelial defects in tissues such as the cornea and the esophagus. Cultured NHEK cells successfully became a stratified squamous cell sheet resembling epithelial tissue, retained expression of cellular integrins and adhesion proteins, and adhered successfully to a type I collagen gel. After culture on the collagen gel, expression of E-cadherin, and b-catenin decreased in the cells of the basal layer of the grafted cell sheet, resembling events characteristic of a partial epithelial–mesenchymal transition (EMT). Cellular events of grafted NHEK cell sheet well as the extracellular matrix (ECM) secreted during culture [5] This retained structure allows transplantable epithelial cell sheets to readily adhere to the wound beds of the esophageal stroma even in the presence of potentially disruptive tissue movements, like the peristaltic movement of the esophagus that accompanies the heartbeat. There is a clear need to better understand how the cell sheet achieves its wound-healing effect
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