TY - JOUR
T1 - Cellular events and behaviors after grafting of stratified squamous epithelial cell sheet onto a hydrated collagen gel
AU - Kasai, Yoshiyuki
AU - Takeda, Naoya
AU - Kobayashi, Shinichiro
AU - Takagi, Ryo
AU - Yamato, Masayuki
N1 - Funding Information:
We acknowledge Prof. Teruo Okano (Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, Japan), who supervised this study and gave us encouragement. Alessondra Speidel and Sebastian Sjo€qvist (Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, Japan) provided useful comments and helped revise this article. This work was supported by the Global Center of Excellence Practical Chemical Wisdom, the Formation of Innovation Center for Fusion of Advanced Technologies in the Special Coordination Funds for Promoting Science and Technology ‘Cell Sheet Tissue Engineering Center (CSTEC)’ and the Global Center of Excellence program, the Multidisciplinary Education and Research Center for the Establishment of Regenerative Medicine (MERCREM), from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) Japan. Financial support of a grant-in-aid from the framework agreement between the Faculty of Science and Engineering, Waseda University and Mitsubishi Materials Corp, and Misao Yanag-ihara’s Research fellowship awarded by the Academy of Future Medicine are also acknowledged.
Funding Information:
Masayuki Yamato is a stakeholder of CellSeed Inc. Tokyo Women’s Medical University receives research funding from CellSeed Inc.
Funding Information:
We acknowledge Prof. Teruo Okano (Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan), who supervised this study and gave us encouragement. Alessondra Speidel and Sebastian Sjöqvist (Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan) provided useful comments and helped revise this article. This work was supported by the Global Center of Excellence Practical Chemical Wisdom, the Formation of Innovation Center for Fusion of Advanced Technologies in the Special Coordination Funds for Promoting Science and Technology ‘Cell Sheet Tissue Engineering Center (CSTEC)’ and the Global Center of Excellence program, the Multidisciplinary Education and Research Center for the Establishment of Regenerative Medicine (MERCREM), from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) Japan. Financial support of a grant-in-aid from the framework agreement between the Faculty of Science and Engineering, Waseda University and Mitsubishi Materials Corp, and Misao Yanagihara's Research fellowship awarded by the Academy of Future Medicine are also acknowledged.
Publisher Copyright:
© 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
KW - collective cell migration
KW - grafting
KW - partial EMT
KW - regenerative therapy
KW - stratified squamous epithelial cell sheet
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U2 - 10.1002/2211-5463.12213
DO - 10.1002/2211-5463.12213
M3 - Article
AN - SCOPUS:85016597030
SN - 2211-5463
VL - 7
SP - 691
EP - 704
JO - FEBS Open Bio
JF - FEBS Open Bio
IS - 5
ER -