スダ　サトシ   SUDA Satoshi   須田　智    所属   埼玉医科大学  医学部 国際医療センター　神経内科・脳卒中内科    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	Mesenchymal Stem Cells Overexpressing Interleukin-10 Promote Neuroprotection in Experimental Acute Ischemic Stroke
掲載誌名	正式名：MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT ISSNコード：2329-0501
出版社	CELL PRESS
巻・号・頁	6,102-111頁
著者・共著者	Masataka Nakajima,Chikako Nito,Kota Sowa,Satoshi Suda,Yasuhiro Nishiyama,Aki Nakamura-Takahashi,Yuko Nitahara-Kasahara,Kiwamu Imagawa,Tohru Hirato,Masayuki Ueda,Kazumi Kimura,Takashi Okada
発行年月	2017/09
概要	Interleukin (IL)-10 is a contributing factor to neuroprotection of mesenchymal stem cell (MSC) transplantation after ischemic stroke. Our aim was to increase therapeutic effects by combining MSCs and ex vivo IL-10 gene transfer with an adeno-associated virus (AAV) vector using a rat transient middle cerebral artery occlusion (MCAO) model. SpragueDawley rats underwent 90 min MCAO followed by intravenous administration of MSCs alone or IL-10 gene-transferred MSCs (MSC/IL-10) at 0 or 3 hr after ischemia reperfusion. Infarct lesions, neurological deficits, and immunological analyses were performed within 7 days after MCAO. 0-hr transplantation of MSCs alone and MSC/IL-10 significantly reduced infarct volumes and improved motor function. Conversely, 3-hr transplantation of MSC/IL-10, but not MSCs alone, significantly reduced infarct volumes (p < 0.01) and improved motor function (p < 0.01) compared with vehicle groups at 72 hr and 7 days after MCAO. Immunological analysis showed that MSC/IL-10 transplantation significantly inhibits microglial activation and pro-inflammatory cytokine expression compared with MSCs alone. Moreover, overexpressing IL-10 suppressed neuronal degeneration and improved survival of engrafted MSCs in the ischemic hemisphere. These results suggest that overexpressing IL-10 enhances the neuroprotective effects of MSC transplantation by anti-inflammatory modulation and thereby supports neuronal survival during the acute ischemic phase.
DOI	10.1016/j.omtm.2017.06.005
PMID	28725658