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	Cellular interactions in cell sheets enhance mesenchymal stromal cell immunomodulatory properties.
掲載誌名	正式名：Tissue engineering. Part A 略　 称：Tissue Eng Part A ISSNコード：1937335X/19373341
掲載区分	国外
巻・号・頁	29(21-22),pp.594-603
著者・共著者	Dunn Celia M, KAMEISHI Sumako, Parker Tavie, Cho Yun-Kyoung, Song Sun U, Grainger David W, OKANO Teruo
発行年月	2023/10
概要	Immune-related applications of mesenchymal stromal cells (MSCs) in cell therapy seek to exploit immunomodulatory paracrine signaling pathways to reduce inflammation. A key MSC therapeutic challenge is reducing patient outcome variabilities attributed to insufficient engraftment/retention of injected heterogenous MSCs. To address this, we propose directly transplantable human single-cell-derived clonal bone marrow MSC (cBMSC) sheets. Cell sheet technology is a scaffold-free tissue engineering strategy enabling scalable production of highly engraftable cell constructs retaining endogenous cell-cell and -matrix interactions, important to cell function. cBMSCs, as unique MSC subset populations, facilitate rational selection of therapeutically relevant MSC clones from donors. Here, we combine human cBMSCs with cell sheet technology, demonstrating cell sheet fabrication as a method to significantly upregulate the expression of immunomodulatory molecules IL-10, IDO-1, and PTGES2 across GMP-grade hcBMSC lines and whole hBMSCs compared to respective conventional cell suspensions. When treated with carbenoxolone, a gap junction inhibitor, cell sheets downregulate IL-10 and IDO-1 expression, implicating functional roles for intercellular sheet interactions. Beyond producing directly transferable multi-cellular hcBMSC constructs, cell sheet technology amplifies hcBMSC expression of immunomodulatory factors important to therapeutic action. Additionally, this work demonstrates the importance of cell-cell interactions as a tissue engineering design criterion to enhance consistent MSC functions.
DOI	10.1089/ten.TEA.2023.0059
PMID	37847176