Cellular events and behaviors after grafting of stratified squamous epithelial cell sheet onto a hydrated collagen gel

• Published in: FEBS open bio Vol. 7; no. 5; pp. 691 - 704
• Main Authors: Kasai, Yoshiyuki, Takeda, Naoya, Kobayashi, Shinichiro, Takagi, Ryo, Yamato, Masayuki
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2017; John Wiley and Sons Inc
• Subjects: Autografts; Basal cells; Biomedical engineering; Cell adhesion & migration; Cell culture; Collagen; Collagen (type I); collective cell migration; Cornea; Endoscopy; Engineering; Epithelial cells; Esophagus; grafting; Growth factors; Integrins; Mesenchyme; partial EMT; Proteins; regenerative therapy; Scholarships & fellowships; Science; stratified squamous epithelial cell sheet; Women; Wound healing; United States > US; Japan; collective cell migration; partial EMT; stratified squamous epithelial cell sheet; grafting; regenerative therapy
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.12213

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. We created an in vitro grafting model using cultured normal human epidermal keratinocyte (NHEK) sheets and a type I collagen gel. After adhesion on the collagen gel, expression of E‐cadherin and β‐catenin decreased in the cells of the basal layer of the grafted cell sheet, events characteristic of partial epithelial‐mesenchymal transition (EMT). These basal cells also induced migration of the cell sheet. These phenomena are consistent with essential events that occur in wound healing processes observed previously in cell studies.