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	査読なし
表題	Interferon-Gamma Primed Human Clonal Mesenchymal Stromal Cell Sheets Exhibit Enhanced Immunosuppressive Function.
掲載誌名	正式名：Cells 略　 称：Cells ISSNコード：20734409/20734409
掲載区分	国外
巻・号・頁	11(23),pp.3788
国際共著	国際共著
著者・共著者	Celia M Dunn, Sumako Kameishi, Yun-Kyoung Cho, Sun U Song, David W Grainger, Teruo Okano
担当区分	最終著者
発行年月	2022/11
概要	Mesenchymal stromal cells (MSCs) represent a promising treatment for immune-related diseases due to their diverse immunomodulatory paracrine functions. However, progress of culture-expanded MSCs is hindered by inconsistent cell function, poor localization, and insufficient retention when administered as suspended cell injections, thus placing spatiotemporal dosing constraints on therapeutic functions. To address these limitations, we introduce the combination of in vitro interferon-gamma (IFN-γ) priming, a key stimulator of MSC immunosuppressive potency, and thermoresponsive cultureware to harvest cultured MSCs as directly transplantable scaffold-free immunosuppressive cell sheets. Here, we demonstrate that MSC sheets produced with IFN-γ priming upregulate expression of immunosuppressive factors indoleamine 2,3-dioxygenase (IDO-1), interleukin-10 (IL-10), programmed death ligand-1 (PD-L1), and prostaglandin E2 (PGE2) in both dose- and duration-dependent manners. In addition, IFN-γ primed MSC sheets showed increased ability to inhibit T-cell proliferation via indirect and direct contact, specifically related to increased IDO-1 and PGE2 concentrations. Furthermore, this study's use of human clinical-grade single-cell-derived clonal bone marrow-derived MSCs, contributes to the future translatability and clinical relevancy of the produced sheets. Ultimately, these results present the combination of IFN-γ priming and MSC sheets as a new strategy to improve MSC-mediated treatment of localized inflammatory diseases.
DOI	10.3390/cells11233738
PMID	36497001