オカノ　テルオ   OKANO Teruo   岡野　光夫    所属   研究施設 研究施設    職種   特任顧問
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Phenotypic traits of mesenchymal stem cell sheets fabricated by temperature-responsive cell culture plate: structural characteristics of MSC sheets.
掲載誌名	正式名：Stem cell research & therapy 略　 称：Stem Cell Res Ther ISSNコード：17576512/17576512
掲載区分	国外
出版社	Springer
巻・号・頁	10(1),pp.353
著者・共著者	NAKAO Mitsuyoshi†, KIM Kyungsook*, NAGASE Kenichi, GRAINGER David W, KANAZAWA Hideko, OKANO Teruo*
担当区分	最終著者,責任著者
発行年月	2019/11/28
概要	BACKGROUND:In most stem cell therapy strategies reported to date, stem cells are introduced to damaged tissue sites to repair and regenerate the original tissue structure and function. MSC therapeutic efficacies are inconsistent, largely attributed to transplanted MSC difficulties both in engrafting at tissue sites and in retaining their therapeutic functions from suspension formulations. MSC functional components, including cell adhesion and cell-cell junction proteins, and ECM that contribute to essential cellular therapeutic effects, are damaged or removed by proteolytic enzymes used in stem cell harvesting strategies from culture. To overcome these limitations, methods to harvest and transplant cells without disrupting critical stem cell functions are required. Cell sheet technology, exploiting temperature-responsive cell culture surfaces, permits cell harvest without cell protein damage. This study is focused on phenotypic traits of MSC sheets structurally and functionally to understand therapeutic benefits of cell sheets.METHODS/RESULTS:This study verified cleaved cellular proteins (vinculin, fibronectin, laminin, integrin β-1, and connexin 43) and increased apoptotic cell death produced under standard trypsin harvesting treatment in a time-dependent manner. However, MSC sheets produced without trypsin using only temperature-controlled sheet harvest from culture plastic exhibited intact cellular structures. Also, MSCs harvested using enzymatic treatment (i.e., chemical disruption) showed higher pYAP expression compared to MSC sheets.CONCLUSION:Retention of cellular structures such as ECM, cell-cell junctions, and cell-ECM junctions is correlated with human umbilical cord mesenchymal stem cell (hUC-MSC) survival after detachment from cell culture surfaces. Retaining these proteins intact in MSC cultures using cell sheet technology is proposed to enhance stem cell survival and their function in stem cell-based therapy.
DOI	10.1186/s13287-019-1431-6
PMID	31779694