ID | 64351 |
フルテキストURL | |
著者 |
Yabuno, Satoru
Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yasuhara, Takao
Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Nagase, Takayuki
Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kawauchi, Satoshi
Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Sugahara, Chiaki
Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Okazaki, Yosuke
Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hosomoto, Kakeru
Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Sasada, Susumu
Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Sasaki, Tatsuya
Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Tajiri, Naoki
Department of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Sciences and Medical School
Borlongan, Cesar V.
Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida
Date, Isao
Department of Neurological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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抄録 | Background Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke.
Methods Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 x 10(5) cells/5 mu l) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups. Results SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05). Conclusions This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF. |
キーワード | Cerebral ischemic infarct
Rehabilitation
Regenerative medicine
SB623
Voluntary exercise
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発行日 | 2023-01-24
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出版物タイトル |
STEM Cell Research & Therapy
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巻 | 14巻
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号 | 1号
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出版者 | BMC
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開始ページ | 10
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ISSN | 1757-6512
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © The Author(s) 2023.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1186/s13287-023-03236-4
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ライセンス | http://creativecommons.org/licenses/by/4.0/
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Citation | Yabuno, S., Yasuhara, T., Nagase, T. et al. Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke. Stem Cell Res Ther 14, 10 (2023). https://doi.org/10.1186/s13287-023-03236-4
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助成機関名 |
Japan Society for the Promotion of Science
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助成番号 | 22K09207
22K09285
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