オカノ　テルオ   Okano Teruo   岡野　光夫    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   評議員
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Enhancing chondrogenic potential via mesenchymal stem cell sheet multilayering.
掲載誌名	正式名：Regenerative Therapy ISSNコード：2352-3204
掲載区分	国外
巻・号・頁	18,pp.487-496
著者・共著者	THORP Halie†, KIM Kyungsook*, BOU-GHANNAM Sophia, KONDO Makoto, MAAK Travis, GRAINGER David W., OKANO Teruo*
担当区分	責任著者
発行年月	2021/12
概要	Advanced tissue engineering approaches for direct articular cartilage replacement in vivo employ mesenchymal stem cell (MSC) sources, exploiting innate chondrogenic potential to fabricate hyaline-like constructs in vitro within three-dimensional (3D) culture conditions. Cell sheet technology represents one such advanced 3D scaffold-free cell culture platform, and previous work has shown that 3D MSC sheets are capable of in vitro hyaline-like chondrogenic differentiation. The present study aims to build upon this understanding and elucidate the effects of an established cell sheet manipulation technique, cell sheet multilayering, on fabrication of MSC-derived hyaline-like cartilage 3D layered constructs in vitro. To achieve this goal, multilayered MSC sheets are prepared and assessed for structural and biochemical transitions throughout chondrogenesis. Results support MSC multilayering as a means of increasing construct thickness and 3D cellular interactions related to in vitro chondrogenesis, including N-cadherin, connexin 43, and integrin β-1. Data indicate that increasing construct thickness from 14 μm (1-layer construct) to 25 μm (2-layer construct) increases these cellular interactions and subsequent in vitro MSC chondrogenesis. However, a clear initial thickness threshold (33 μm - 3-layer construct) is evident that decreases the rate and extent of in vitro chondrogenesis, specifically chondrogenic gene expressions (Sox9, aggrecan, type II collagen) and sulfated proteoglycan accumulation in deposited extracellular matrix (ECM). Together, these data support the utility of cell sheet multilayering as a platform for tailoring construct thickness and subsequent MSC chondrogenesis for future articular cartilage regeneration applications.
DOI	10.1016/j.reth.2021.11.004
PMID	34926734