論文

査読有り
2017年9月

Mesenchymal Stem Cells Overexpressing Interleukin-10 Promote Neuroprotection in Experimental Acute Ischemic Stroke

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
  • 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

6
開始ページ
102
終了ページ
111
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.omtm.2017.06.005
出版者・発行元
CELL PRESS

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.

Web of Science ® 被引用回数 : 38

リンク情報
DOI
https://doi.org/10.1016/j.omtm.2017.06.005
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28725658
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000410660600012&DestApp=WOS_CPL

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