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	Combination therapy with bone marrow stromal cells and FK506 enhanced amelioration of ischemic brain damage in rats
掲載誌名	正式名：LIFE SCIENCES ISSNコード：0024-3205
出版社	PERGAMON-ELSEVIER SCIENCE LTD
巻・号・頁	89(1-2),50-56頁
著者・共著者	Satoshi Suda,Kuniko Shimazaki,Masayuki Ueda,Toshiki Inaba,Nobuo Kamiya,Ken-ichiro Katsura,Yasuo Katayama
発行年月	2011/07
概要	Aims: Transplantation of bone marrow stromal cells (MSCs) has been shown to ameliorate ischemic brain injury in animals. In the present study, we investigated whether the transplantation of MSCs combined with FK506, a clinically used immunosuppressant, enhanced neuroprotective effects in rat experimental stroke. Main methods: Male Sprague-Dawley rats underwent transient 90 min middle cerebral artery occlusion (MCAO). Two or 6 h after ischemia onset, the rats were randomly assigned to receive intravenous administration of MSCs plus FK506, MSCs alone, FK506 alone, or vehicle. Infarct volume, and neurological and immunohistological assessments were performed to examine the effects of these therapies. Key findings: In 2-hour post-ischemia treatment groups, significant improvement of infarct volume and neurological scores were observed 1 day after combination therapy compared with monotherapy, and this neuroprotection continued for 7 days. Combination therapy significantly reduced the number of TUNEL-positive apoptotic cells, increased Bcl-2 expression, decreased Bax expression, and suppressed neutrophil infiltration and microglia/macrophage activation compared to monotherapy. In 6-hour post-ischemia treatment groups, a significant reduction of infarct volume, edema index, and neurological score was observed only in the combination therapy group. Moreover, the number of engrafted MSCs on day 7 with combination therapy was significantly higher than with MSCs alone. Significance: Combination therapy using FK506 enhanced the anti-apoptotic and anti-inflammatory effects of MSCs and increased the survival of transplanted cells, leading to expansion of the therapeutic time window for MSCs. (C) 2011 Elsevier Inc. All rights reserved.
DOI	10.1016/j.lfs.2011.05.001
PMID	21620871