OKANO Teruo
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position  
Article types Original article
Language English
Peer review Peer reviewed
Title Cellular interactions in cell sheets enhance mesenchymal stromal cell immunomodulatory properties.
Journal Formal name：Tissue engineering. Part A
Abbreviation：Tissue Eng Part A
ISSN code：1937335X/19373341
Domestic / ForeginForegin
Volume, Issue, Page 29(21-22),pp.594-603
Author and coauthor Dunn Celia M, KAMEISHI Sumako, Parker Tavie, Cho Yun-Kyoung, Song Sun U, Grainger David W, OKANO Teruo
Publication date 2023/10
Summary 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