Updated on 2025/08/22

写真a

 
NAKAZAKI Kimihito
 
Organization
Funded Projects Advanced Regenerative Therapeuics Special-Appoingment Lecturer
Title
Special-Appoingment Lecturer
Homepage
https://web.sapmed.ac.jp/regeneration/staff.php
ORCID ID
0000-0003-3155-5116
External link

Research Areas

  • Life Science / Neurosurgery

  • Life Science / Neuroscience-general

  • Life Science / Orthopedics

Research History

  • Sapporo Medical University   School of Medicine

    2025.4

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  • Yale University   School of Medicine

    2024.4

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  • Sapporo Medical University

    2024.4 - 2025.3

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  • Yale University   Associate Research Scientist

    2022.9 - 2024.4

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  • Yale University   Postdoctoral Associate

    2018.9 - 2021.8

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  • Sapporo Medical University

    2013.4 - 2018.8

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Papers

  • Mesenchymal Stem Cells and Their Extracellular Vesicles: Therapeutic Mechanisms for Blood–Spinal Cord Barrier Repair Following Spinal Cord Injury

    Masahito Nakazaki, Takahiro Yokoyama, Karen L. Lankford, Ryosuke Hirota, Jeffery D. Kocsis, Osamu Honmou

    International Journal of Molecular Sciences   2024.12

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    Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)  

    DOI： 10.3390/ijms252413460

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  • Human mesenchymal stem-derived extracellular vesicles improve body growth and motor function following severe spinal cord injury in rat. International journal

    Masahito Nakazaki, Karen L Lankford, Hideaki Yamamoto, Yoshiyuki Mae, Jeffery D Kocsis

    Clinical and translational medicine   13 ( 6 )   e1284   2023.6

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Spinal cord injury (SCI) in young adults leads to severe sensorimotor disabilities as well as slowing of growth. Systemic pro-inflammatory cytokines are associated with growth failure and muscle wasting. Here we investigated whether intravenous (IV) delivery of small extracellular vesicles (sEVs) derived from human mesenchymal stem/stromal cells (MSC) has therapeutic effects on body growth and motor recovery and can modulate inflammatory cytokines following severe SCI in young adult rats. METHODS: Contusional SCI rats were randomized into three different treatment groups (human and rat MSC-sEVs and a PBS group) on day 7 post-SCI. Functional motor recovery and body growth were assessed weekly until day 70 post-SCI. Trafficking of sEVs after IV infusions in vivo, the uptake of sEVs in vitro, macrophage phenotype at the lesion and cytokine levels at the lesion, liver and systemic circulation were also evaluated. RESULTS: An IV delivery of both human and rat MSC-sEVs improved functional motor recovery after SCI and restored normal body growth in young adult SCI rats, indicating a broad therapeutic benefit of MSC-sEVs and a lack of species specificity for these effects. Human MSC-sEVs were selectively taken up by M2 macrophages in vivo and in vitro, consistent with our previous observations of rat MSC-sEV uptake. Furthermore, the infusion of human or rat MSC-sEVs resulted in an increase in the proportion of M2 macrophages and a decrease in the production of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-6 at the injury site, as well as a reduction in systemic serum levels of TNF-α and IL-6 and an increase in growth hormone receptors and IGF-1 levels in the liver. CONCLUSIONS: Both human and rat MSC-sEVs promote the recovery of body growth and motor function after SCI in young adult rats possibly via the cytokine modulation of growth-related hormonal pathways. Thus, MSC-sEVs affect both metabolic and neurological deficits in SCI.

    DOI： 10.1002/ctm2.1284

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  • Small extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF-β upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury. International journal

    Masahito Nakazaki, Tomonori Morita, Karen L Lankford, Philip W Askenase, Jeffery D Kocsis

    Journal of extracellular vesicles   10 ( 11 )   e12137   2021.9

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Intravenous (IV) infusion of bone marrow-derived mesenchymal stem/stromal cells (MSCs) stabilizes the blood-spinal cord barrier (BSCB) and improves functional recovery in experimental models of spinal cord injury (SCI). Although IV delivered MSCs do not traffic to the injury site, IV delivered small extracellular vesicles (sEVs) derived from MSCs (MSC-sEVs) do and are taken up by a subset of M2 macrophages. To test whether sEVs released by MSCs are responsible for the therapeutic effects of MSCs, we tracked sEVs produced by IV delivered DiR-labelled MSCs (DiR-MSCs) after transplantation into SCI rats. We found that sEVs were released by MSCs in vivo, trafficked to the injury site, associated specifically with M2 macrophages and co-localized with exosome markers. Furthermore, while a single MSC injection was sufficient to improve locomotor recovery, fractionated dosing of MSC-sEVs over 3 days (F-sEVs) was required to achieve similar therapeutic effects. Infusion of F-sEVs mimicked the effects of single dose MSC infusion on multiple parameters including: increased expression of M2 macrophage markers, upregulation of transforming growth factor-beta (TGF-β), TGF-β receptors and tight junction proteins, and reduction in BSCB permeability. These data suggest that release of sEVs by MSCs over time induces a cascade of cellular responses leading to improved functional recovery.

    DOI： 10.1002/jev2.12137

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  • Intravenous infusion of auto serum-expanded autologous mesenchymal stem cells in spinal cord injury patients: 13 case series. International journal

    Osamu Honmou, Toshihiko Yamashita, Tomonori Morita, Tsutomu Oshigiri, Ryosuke Hirota, Satoshi Iyama, Junji Kato, Yuichi Sasaki, Sumio Ishiai, Yoichi M Ito, Ai Namioka, Takahiro Namioka, Masahito Nakazaki, Yuko Kataoka-Sasaki, Rie Onodera, Shinichi Oka, Masanori Sasaki, Stephen G Waxman, Jeffery D Kocsis

    Clinical neurology and neurosurgery   203   106565 - 106565   2021.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Although spinal cord injury (SCI) is a major cause of disability, current therapeutic options remain limited. Recent progress in cellular therapy with mesenchymal stem cells (MSCs) has provided improved function in animal models of SCI. We investigated the safety and feasibility of intravenous infusion of MSCs for SCI patients and assessed functional status after MSC infusion. METHODS: In this phase 2 study of intravenous infusion of autologous MSCs cultured in auto-serum, a single infusion of MSCs under Good Manufacturing Practice (GMP) production was delivered in 13 SCI patients. In addition to assessing feasibility and safety, neurological function was assessed using the American Spinal Injury Association Impairment Scale (ASIA), International Standards for Neurological and Functional Classification of Spinal Cord (ISCSCI-92). Ability of daily living was assessed using Spinal Cord Independence Measure (SCIM-III). The study protocol was based on advice provided by the Pharmaceuticals and Medical Devices Agency in Japan. The trial was registered with the Japan Medical Association (JMA-IIA00154). RESULTS: No serious adverse events were associated with MSC injection. There was neurologic improvement based on ASIA grade in 12 of the 13 patients at six months post-MSC infusion. Five of six patients classified as ASIA A prior to MSC infusion improved to ASIA B (3/6) or ASIA C (2/6), two ASIA B patients improved to ASIA C (1/2) or ASIA D (1/2), five ASIA C patients improved and reached a functional status of ASIA D (5/5). Notably, improvement from ASIA C to ASIA D was observed one day following MSC infusion for all five patients. Assessment of both ISCSCI-92, SCIM-III also demonstrated functional improvements at six months after MSC infusion, compared to the scores prior to MSC infusion in all patients. CONCLUSION: While we emphasize that this study was unblinded, and does not exclude placebo effects or a contribution of endogenous recovery or observer bias, our observations provide evidence supporting the feasibility, safety and functional improvements of infused MSCs into patients with SCI.

    DOI： 10.1016/j.clineuro.2021.106565

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  • Intravenous infusion of mesenchymal stem cells improves impaired cognitive function in a cerebral small vessel disease model. Reviewed International journal

    Nakazaki M, Sasaki M, Kataoka-Sasaki Y, Oka S, Suzuki J, Sasaki Y, Nagahama H, Hashi K, Kocsis JD, Honmou O

    Neuroscience   408   361 - 377   2019.4

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Cerebral small vessel disease (CSVD) is not only a cause of vascular dementia (VD) but also a contributing factor to Alzheimer's disease (AD). The essential pathological feature of CSVD is the disruption of blood-brain barrier (BBB). Dysfunction of BBB due to degeneration of both endothelial cells and pericytes in capillaries leads to neuronal damage and progressive brain atrophy. Moreover, deterioration of amyloid-β (Aβ) clearance due to the failure of the transvascular BBB transport system results in accumulation of Aβ in the brain. Intravenous infusion of mesenchymal stem cells (MSCs) elicits functional recovery in experimental models including stroke and spinal cord injury. One effect of MSCs is to restore disrupted BBB through remodeling of microvasculature. Using spontaneously hypertensive rats (stroke-prone) with impaired cognitive function as a CSVD model, we have shown that infused MSCs has a therapeutic effect for cognitive function. Restoration of BBB function via remodeling of microvasculature and inhibition of Aβ accumulation could inhibit progressive brain atrophy and lead to restore cognitive dysfunction. Gene expression analysis indicated that infused MSCs activates both transforming growth factor-β and angiopoietin 1 signaling pathways and promotes the remodeling of microvasculature. Thus, infused MSCs may represent a novel therapy for both VD and AD.

    DOI： 10.1016/j.neuroscience.2019.04.018

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  • Intravenous infusion of mesenchymal stem cells inhibits intracranial hemorrhage after recombinant tissue plasminogen activator therapy for transient middle cerebral artery occlusion in rats Reviewed International journal

    Masahito Nakazaki, Masanori Sasaki, Yuko Kataoka-Sasaki, Shinichi Oka, Takahiro Namioka, Ai Namioka, Rie Onodera, Junpei Suzuki, Yuichi Sasaki, Hiroshi Nagahama, Takeshi Mikami, Masahiko Wanibuchi, Jeffery D. Kocsis, Osamu Honmou

    Journal of Neurosurgery   127 ( 4 )   1 - 10   2017.1

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.3171/2016.8.jns16240

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  • Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series

    Ryosuke Hirota, Masanori Sasaki, Satoshi Iyama, Kota Kurihara, Ryunosuke Fukushi, Hisashi Obara, Tsutomu Oshigiri, Tomonori Morita, Masahito Nakazaki, Takahiro Namioka, Ai Namioka, Rie Onodera, Yuko Kataoka-Sasaki, Shinichi Oka, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Yusuke Okuma, Reiko Kondo, Ryo Aichi, Satoko Ohmatsu, Noritaka Kawashima, Yoichi M. Ito, Masayoshi Kobune, Kohichi Takada, Sumio Ishiai, Toru Ogata, Atsushi Teramoto, Toshihiko Yamashita, Jeffery D. Kocsis, Osamu Honmou

    Journal of Clinical Medicine   2024.10

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    DOI： 10.3390/jcm13206072

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  • 慢性期重症頭部外傷症例に対する自家骨髄MSC静脈投与

    岡 真一, 八巻 智洋, 佐々木 祐典, 佐々木 優子, 浪岡 隆洋, 浪岡 愛, 中崎 公仁, 竹村 光広, 鵜飼 亮, 横山 貴裕, 小瀧 勝, 岩立 康男, 小林 繁樹, 本望 修

    Journal of Japan Coma Society: JJCS   32 ( 1 )   103 - 103   2024.7

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    Language：Japanese   Publisher：(一社)日本意識障害学会  

    Ichushi

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  • Intravenous infusion of auto-serum-expanded autologous mesenchymal stem cells into chronic severe brain injury patients

    Tomohiro Yamaki, Shinichi Oka, Satoshi Iyama, Masanori Sasaki, Rie Onodera, Yuko Kataoka-Sasaki, Takahiro Namioka, Ai Namioka, Masahito Nakazaki, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Misako Yamaguchi, Marina Fukino, Taro Takazawa, Megumi Hayasaka, Takamitsu Owaku, Mika Funakura, Shinji Onodera, Yoichi M. Ito, Masayoshi Kobune, Junji Kato, Sumio Ishiai, Jeffery D. Kocsis, Masaru Odaki, Yasuo Iwadate, Shigeki Kobayashi, Osamu Honmou

    Interdisciplinary Neurosurgery   36   101927 - 101927   2024.6

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.inat.2023.101927

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  • Pharmacological Difference Between Platelet Aggregations in Cardioembolic Stroke Patients with Direct Oral Anticoagulants: A Pilot Study

    Masahito Nakazaki, Shinichi Oka, Hirotoshi Magota, Ryo Kiyose, Rie Onodera, Ryo Ukai, Yuko Kataoka-Sasaki, Masanori Sasaki, Osamu Honmou

    Journal of Stroke and Cerebrovascular Diseases   31 ( 7 )   106520 - 106520   2022.7

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    Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.jstrokecerebrovasdis.2022.106520

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  • Intravenous Infusion of Mesenchymal Stem Cells Enhances Therapeutic Efficacy of Reperfusion Therapy in Cerebral Ischemia. International journal

    Ryo Kiyose, Masanori Sasaki, Yuko Kataoka-Sasaki, Masahito Nakazaki, Hiroshi Nagahama, Hirotoshi Magota, Shinichi Oka, Ryo Ukai, Mitsuhiro Takemura, Takahiro Yokoyama, Jeffery D Kocsis, Osamu Honmou

    World neurosurgery   149   e160-e169   2021.5

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    OBJECTIVE: Reperfusion therapy is a standard therapeutic strategy for acute stroke. Non-favorable outcomes are thought to partially result from impaired microcirculatory flow in ischemic tissue. Intravenous infusion of mesenchymal stem cells (MSCs) reduces stroke volume and improves behavioral function in stroke. One suggested therapeutic mechanism is the restoration of the microvasculature. The goal of this study was to determine whether infused MSCs enhance the therapeutic efficacy of reperfusion therapy following stroke in rats. METHODS: First, to establish a transient middle cerebral artery occlusion (MCAO) model displaying approximately identical neurologic function and lesion volume as seen in permanent MCAO (pMCAO) at day 7 after stroke induction, we transiently occluded the MCA for 90, 110, and 120 minutes. We found that the 110-minute occlusion met these criteria and was used as the transient MCAO (tMCAO) model. Next, 4 MCAO groups were used to compare the therapeutic efficacy of infused MSCs: (1) pMCAO+vehicle, (2) tMCAO+vehicle, (3) pMCAO+MSC, and (4) tMCAO+MSC. Our ischemic model was a unique ischemic model system in which both pMCAO and tMCAO provided similar outcomes during the study period in the groups without MSC infusion groups. Behavioral performance, ischemic volume, and regional cerebral blood flow (rCBF) using arterial spin labeling-magnetic resonance imaging and histologic evaluation of microvasculature was performed. RESULTS: The behavioral function, rCBF, and restoration of microvasculature were greater in group 4 than in group 3. Thus, infused MSCs facilitated the therapeutic efficacy of MCA reperfusion in this rat model system. CONCLUSIONS: Intravenous infusion of MSCs may enhance therapeutic efficacy of reperfusion therapy.

    DOI： 10.1016/j.wneu.2021.02.056

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  • Prolonged lifespan in a spontaneously hypertensive rat (stroke prone) model following intravenous infusion of mesenchymal stem cells. International journal

    Masahito Nakazaki, Shinichi Oka, Masanori Sasaki, Yuko Kataoka-Sasaki, Hiroshi Nagahama, Kazuo Hashi, Jeffery D Kocsis, Osamu Honmou

    Heliyon   6 ( 12 )   e05833   2020.12

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Intravenous infusion of mesenchymal stem cells (MSCs) has been reported to provide therapeutic efficacy via microvascular remodeling in a spontaneously hypertensive rat. In this study, we demonstrate that intravenous infusion of MSCs increased the survival rate in a spontaneously hypertensive (stroke prone) rat model in which organs including kidney, brain, heart and liver are damaged during aging due to spontaneous hypertension. Gene expression analysis indicated that infused MSCs activates transforming growth factor-β1-smad3/forkhead box O1 signaling pathway. Renal dysfunction was recovered after MSC infusion. Collectively, intravenous infusion of MSC may extend lifespan in this model system.

    DOI： 10.1016/j.heliyon.2020.e05833

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  • AAFITN/ANZSNR 2010 : Asian-Australasian Federation of Interventional and Therapeutic Neuroradiology & Australian & New Zealand Society of Neuroradiology

    Qian Y, Chong W, Rodesch G, Sup Choi I, Miyachi S, terBrugge K, Liu J, Zhang H, McMahon J, Luo C, Srivatanakul K, Kim B, terBrugge K, Cuong T, Tung Y

    Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences   2020.7

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  • Prevention of neointimal hyperplasia induced by an endovascular stent via intravenous infusion of mesenchymal stem cells. Reviewed International journal

    Nakazaki M, Oka S, Sasaki M, Kataoka-Sasaki Y, Onodera R, Komatsu K, Iihoshi S, Hiroura M, Kawaguchi A, Kocsis JD, Honmou O

    Journal of neurosurgery   1 - 13   2019.10

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    OBJECTIVE: In-stent restenosis after percutaneous transluminal angioplasty and stenting (PTAS) due to neointimal hyperplasia is a potential cause of clinical complications, including repeated revascularization and ischemic events. Neointimal hyperplasia induced by an inflammatory response to the stent strut may be a possible mechanism of in-stent restenosis. Intravenous infusion of bone marrow-derived mesenchymal stem cells (MSCs) has been reported to show therapeutic efficacy for cerebral stroke, presumably by an antiinflammatory effect. This study aimed to determine whether MSCs can reduce or prevent neointimal hyperplasia induced by an endovascular stent. METHODS: In this study, two types of bare metal stents were deployed using a porcine (mini-pig) model. One stent was implanted in the common carotid artery (CCA), which is considered quite similar to the human CCA, and the other was inserted in the superficial cervical artery (SCA), which is similar in size to the human middle cerebral artery. Angiographic images, intravascular ultrasound (IVUS) imaging, and microscopic images were used for analysis. RESULTS: Angiographic images and IVUS studies revealed that intravenous infusion of MSCs immediately after deployment of stents prevented in-stent stenosis of the CCA and SCA. Histological analysis also confirmed that inflammatory responses around the stent struts were reduced in both the stented CCA and SCA in the mini-pig. CONCLUSIONS: Intravenous infusion of MSCs inhibited the inflammatory reaction to an implanted stent strut, and prevented progressive neointimal hyperplasia in the stented CCA and SCA in a porcine model. Thus, MSC treatment could attenuate the recurrence of cerebral ischemic events after stenting.

    DOI： 10.3171/2019.7.jns19575

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  • Intravenous infusion of mesenchymal stem cells promotes functional recovery in a rat model of chronic cerebral infarction. Reviewed International journal

    Namioka T, Namioka A, Sasaki M, Kataoka-Sasaki Y, Oka S, Nakazaki M, Onodera R, Suzuki J, Sasaki Y, Nagahama H, Kocsis JD, Honmou O

    Journal of neurosurgery   1 - 8   2018.10

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    OBJECTIVE:
    Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat models of cerebral infarction. Although clinical studies are ongoing, most studies have focused on the acute or subacute phase of stroke. In the present study, MSCs derived from bone marrow of rats were intravenously infused 8 weeks after the induction of a middle cerebral artery occlusion (MCAO) to investigate whether delayed systemic injection of MSCs improves functional outcome in the chronic phase of stroke in rats.

    METHODS:
    Eight weeks after induction of the MCAO, the rats were randomized and intravenously infused with either MSCs or vehicle. Ischemic volume and behavioral performance were examined. Blood-brain barrier (BBB) integrity was assessed by quantifying the leakage of Evans blue into the brain parenchyma after intravenous infusion. Immunohistochemical analysis was also performed to evaluate the stability of the BBB.

    RESULTS:
    Motor recovery was better in the MSC-treated group than in the vehicle-treated group, with rapid improvement (evident at 1 week post-infusion). In MSC-treated rats, reduced BBB leakage and increased microvasculature/repair and neovascularization were observed.

    CONCLUSIONS:
    These results indicate that the systemic infusion of MSCs results in functional improvement, which is associated with structural changes in the chronic phase of cerebral infarction, including in the stabilization of the BBB.

    DOI： 10.3171/2018.5.jns18140

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  • Intravenous infusion of mesenchymal stem cells for protection against brainstem infarction in a persistent basilar artery occlusion model in the adult rat. Reviewed International journal

    Namioka A, Namioka T, Sasaki M, Kataoka-Sasaki Y, Oka S, Nakazaki M, Onodera R, Suzuki J, Sasaki Y, Nagahama H, Kocsis JD, Honmou O

    Journal of neurosurgery   1 - 9   2018.10

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    OBJECTIVE: Morbidity and mortality in patients with posterior circulation stroke remains an issue despite advances in acute stroke therapies. The intravenous infusion of mesenchymal stem cells (MSCs) elicits therapeutic efficacy in experimental supratentorial stroke models. However, since there are few reliable animal models of ischemia in the posterior circulation, the therapeutic approach with intravenous MSC infusion has not been tested. The objective of this study was to test the hypothesis that intravenously infused MSCs provide functional recovery in a newly developed model of brainstem infarction in rats.

    METHODS: Basilar artery (BA) occlusion (BAO) was established in rats by selectively ligating 4 points of the proximal BA with 10-0 nylon monofilament suture. The intravenous infusion of MSCs was performed 1 day after BAO induction. MRI and histological examinations were performed to assess ischemic lesion volume, while multiple behavioral tests were performed to evaluate functional recovery.

    RESULTS: The MSC-treated group exhibited a greater reduction in ischemic lesion volume, while behavioral testing indicated that the MSC-infused group had greater improvement than the vehicle group 28 days after the MSC infusion. Accumulated infused MSCs were observed in the ischemic brainstem lesion.

    CONCLUSIONS: Infused MSCs may provide neuroprotection to facilitate functional outcomes and reduce ischemic lesion volume as evaluated in a newly developed rat model of persistent BAO.

    DOI： 10.3171/2018.4.jns173121

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  • 脊髄損傷患者に対する自家培養骨髄間葉系幹細胞(MSC)の静脈投与におけるDTI-MRIを用いた脊髄・脳plasticity解析

    岡 真一, 廣田 亮介, 押切 勉, 森田 智慶, 長濱 宏史, 中崎 公仁, 佐々木 優子, 佐々木 祐典, 本望 修, 山下 敏彦

    日本整形外科学会雑誌   92 ( 8 )   S1840 - S1840   2018.8

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  • Functional recovery after the systemic administration of mesenchymal stem cells in a rat model of neonatal hypoxia-ischemia. Reviewed International journal

    Sakai T, Sasaki M, Kataoka-Sasaki Y, Oka S, Nakazaki M, Fukumura S, Kobayashi M, Tsutsumi H, Kocsis JD, Honmou O

    Journal of neurosurgery. Pediatrics   22 ( 5 )   513 - 522   2018.8

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    The authors intravenously infused mesenchymal stem cells (MSCs) into a rat model of neonatal hypoxia-ischemia and found improvements in functional outcome, increased brain volume, and enhanced synaptogenesis. The results of this animal study suggest that the intravenous administration of MSCs should be further explored as a potential treatment for patients suffering from cerebral palsy after hypoxic-ischemic encephalopathy.

    DOI： 10.3171/2018.5.peds1845

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  • Intravenous Infusion of Mesenchymal Stem Cells Alters Motor Cortex Gene Expression in a Rat Model of Acute Spinal Cord Injury. Reviewed International journal

    Oshigiri T, Sasaki T, Sasaki M, Kataoka-Sasaki Y, Nakazaki M, Oka S, Morita T, Hirota R, Yoshimoto M, Yamashita T, Hashimoto-Torii K, Honmou O

    Journal of neurotrauma   36 ( 3 )   411 - 420   2018.8

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    Recent evidence has demonstrated that remote responses in the brain, as well as local responses in the injured spinal cord, can be induced after spinal cord injury (SCI). Intravenous infusion of mesenchymal stem cells (MSCs) has been shown to provide functional improvements in SCI through local therapeutic mechanisms that provide neuroprotection, stabilization of the blood-spinal cord barrier, remyelination, and axonal sprouting. In the present study, we examined the brain response that might be associated with the functional improvements induced by the infused MSCs after SCI. Genome-wide RNA profiling was performed in the motor cortex of SCI rats at 3 days post-MSC or vehicle infusion. Then, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) data revealed that the "behaviorally-associated differentially expressed genes (DEGs)" were identified by the Pearson's correlation analysis with the behavioral function, suggesting that the "behaviorally-associated DEGs" may be related to the functional recovery after systemic infusion of MSCs in SCI. These results suggested that the infused MSCs alter the gene expression signature in the brain and that these expression changes may contribute to the improved function in SCI.

    DOI： 10.1089/neu.2018.5793

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  • 放射線技術学を用いた先端生命科学研究 前臨床MRIを用いた脳梗塞に対する再生治療メカニズムの評価

    長濱 宏史, 鈴木 淳平, 佐々木 祐典, 中崎 公仁, 本望 修

    日本放射線技術学会雑誌   74 ( 7 )   722 - 725   2018.7

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  • Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats. Reviewed International journal

    Matsuda Y, Sasaki M, Kataoka-Sasaki Y, Takayanagi A, Kobayashi K, Oka S, Nakazaki M, Masumori N, Kocsis JD, Honmou O

    Sexual medicine   6 ( 1 )   49 - 57   2018.3

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    INTRODUCTION: Intravenous preload (delivered before cavernous nerve [CN] injury) of bone marrow-derived mesenchymal stem cells (MSCs) can prevent or decrease postoperative erectile dysfunction (J Sex Med 2015;12:1713-1721). In the present study, the potential therapeutic effects of intravenously administered MSCs on postoperative erectile dysfunction were evaluated in a rat model of CN injury. METHODS: Male Sprague-Dawley rats were randomized into 2 groups after electric CN injury. Intravenous infusion of bone marrow-derived MSCs (1.0 × 106 cells in Dulbecco's modified Eagle's medium 1 mL) or vehicle (Dulbecco's modified Eagle's medium 1 mL) was performed 3 hours after electrocautery-induced CN injury. MAIN OUTCOME MEASURES: To assess erectile function, we measured intracavernous pressure at 4 weeks after MSC or vehicle infusion. Histologic examinations were performed to investigate neuronal innervation and inhibition of smooth muscle atrophy. Green fluorescent protein-positive bone marrow-derived MSCs were used for cell tracking. To investigate mRNA expression levels of neurotrophins in the major pelvic ganglia (MPGs), quantitative real-time polymerase chain reaction was performed. RESULTS: The decrease of intracavernous pressure corrected for arterial pressure and area under the curve of intracavernous pressure in the bone marrow-derived MSC group was significantly lower than that in the vehicle group at 4 weeks after infusion (P < .05). Retrograde neuronal tracing indicated that the MSC group had a larger number of FluoroGold-positive neurons in the MPGs compared with the vehicle group. The ratio of smooth muscle to collagen in the MSC group was significantly higher than in the vehicle group. Green fluorescent protein-positive bone marrow-derived MSCs were detected in the MPGs and injured CNs using confocal microscopy, indicating homing of cells to the MPGs and injured CNs. Brain-derived neurotrophic factor and glial cell-derived neurotrophic factor expression levels in the MPGs were significantly higher in the MSC group than in the vehicle group (P < .01). CONCLUSION: Intravenous infusion of bone marrow-derived MSCs after CN injury might have therapeutic efficacy in experimental erectile dysfunction. Matsuda Y, Sasaki M, Kataoka-Sasaki Y, et al. Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats. Sex Med 2018;6:49-57.

    DOI： 10.1016/j.esxm.2017.10.005

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  • Intravenous infusion of mesenchymal stem cells reduces epileptogenesis in a rat model of status epilepticus. Reviewed International journal

    Fukumura S, Sasaki M, Kataoka-Sasaki Y, Oka S, Nakazaki M, Nagahama H, Morita T, Sakai T, Tsutsumi H, Kocsis JD, Honmou O

    Epilepsy research   141   56 - 63   2018.2

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    DOI： 10.1016/j.eplepsyres.2018.02.008

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  • [8. Evaluation of the Therapeutic Mechanisms in Regeneration Therapy for Cerebral Infarction Using Pre-clinical Magnetic Resonance Imaging]. Reviewed

    Nagahama H, Suzuki J, Sasaki M, Nakazaki M, Honmou O

    Nihon Hoshasen Gijutsu Gakkai zasshi   74 ( 7 )   722 - 725   2018.1

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    DOI： 10.6009/jjrt.2018_jsrt_74.7.722

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  • Cerebral aneurysm neck diameter is an independent predictor of progressive occlusion after stent-assisted coiling Reviewed International journal

    Masahito Nakazaki, Tadashi Nonaka, Tatsufumi Nomura, Toshiyuki Onda, Yasuyuki Yonemasu, Akira Takahashi, Yuji Hashimoto, Osamu Honda, Shinichi Oka, Masanori Sasaki, Masahiko Daibo, Osamu Honmou

    Acta Neurochirurgica   159 ( 7 )   1313 - 1319   2017.7

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    DOI： 10.1007/s00701-017-3199-8

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  • Elevated brain derived neurotrophic factor (BDNF) levels in plasma but not serum reflect in vivo functional viability of infused mesenchymal stem cells after middle cerebral artery occlusion in rat. Reviewed International journal

    Nakamura H, Sasaki Y, Sasaki M, Kataoka-Sasaki Y, Oka S, Nakazaki M, Namioka T, Namioka A, Onodera R, Suzuki J, Nagahama H, Mikami T, Wanibuchi M, Kocsis JD, Honmou O

    Journal of neurosurgical sciences   63 ( 1 )   42 - 49   2017.2

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    Nakamura H, Sasaki Y, Sasaki M, Kataoka-Sasaki Y, Oka S, Nakazaki M, Namioka T, Namioka A, Onodera R, Suzuki J, Nagahama H, Mikami T, Wanibuchi M, Kocsis JD, Honmou O, Journal of neurosurgical sciences, 2017, 2017

    DOI： 10.23736/s0390-5616.17.03989-3

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  • Synergic Effects of Rehabilitation and Intravenous Infusion of Mesenchymal Stem Cells After Stroke in Rats. Reviewed International journal

    Sasaki Y, Sasaki M, Kataoka-Sasaki Y, Nakazaki M, Nagahama H, Suzuki J, Tateyama D, Oka S, Namioka T, Namioka A, Onodera R, Mikami T, Wanibuchi M, Kakizawa M, Ishiai S, Kocsis JD, Honmou O

    PHYSICAL THERAPY   96 ( 11 )   1791 - 1798   2016.11

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    DOI： 10.2522/ptj.20150504

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  • Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury. Reviewed International journal

    Morita T, Sasaki M, Kataoka-Sasaki Y, Nakazaki M, Nagahama H, Oka S, Oshigiri T, Takebayashi T, Yamashita T, Kocsis JD, Honmou O

    NEUROSCIENCE   335   221 - 231   2016.10

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    DOI： 10.1016/j.neuroscience.2016.08.037

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  • Double balloon protection during carotid artery stenting for vulnerable carotid stenosis reduces the incidence of new brain lesions Reviewed International journal

    Masahito Nakazaki, Tadashi Nonaka, Akira Takahashi, Yasuyuki Yonemasu, Tatsufumi Nomura, Toshiyuki Onda, Osamu Honda, Yuji Hashimoto, Hirofumi Ohnishi, Masanori Sasaki, Masahiko Daibo, Osamu Honmou

    Acta Neurochirurgica   158 ( 7 )   1377 - 1386   2016.5

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    DOI： 10.1007/s00701-016-2816-2

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  • [Treatment of cerebral ischemia using mesenchymal stem cell-clinical trial phase III]. Reviewed

    Nakazaki M, Oka S, Sasaki M, Honmou O

    118 ( 2 )   93 - 97   2015.2

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    Authorship：Lead author   Publishing type：Research paper (scientific journal)  

    Nakazaki M, Oka S, Sasaki M, Honmou O, Nihon Jibiinkoka Gakkai kaiho, 2015, vol. 118, no. 2, pp. 93-97

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  • 他領域からのトピックス 脳梗塞後遺症の機能回復を目指した,骨髄間葉系幹細胞治療 : 医師主導治験Phase Ⅲ

    Nippon Jibiinkoka Gakkai Kaiho   118 ( 2 )   93 - 97   2015

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    Language：Japanese   Publisher：The Oto-Rhino-Laryngological Society of Japan, Inc.  

    Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I026196808

    DOI： 10.3950/jibiinkoka.118.93

    CiNii Research

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  • ラット脳梗塞モデルに対する骨髄間葉系幹細胞移植後のfMRI による皮質賦活信号と運動機能改善との関連性 Reviewed

    Masahito Nakazaki, Junpei Suzuki, Masanori Sasaki, Shinichi Oka, Yuko Sasaki, Osamu Honmou

    Cerebral Blood Flow and Metabolism   25 ( 2 )   67 - 71   2014

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    DOI： 10.16977/cbfm.25.2_67

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  • [Retrospective analysis of the effectiveness of Yokukansan(Japanese Herbal Medicine, TJ-54)in the treatment of delirium following acute stroke]. Reviewed

    Nakazaki M, Mori T, Iwata T, Miyazaki Y, Takahashi Y

    No shinkei geka. Neurological surgery   41 ( 9 )   765 - 771   2013.9

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    Nakazaki M, Mori T, Iwata T, Miyazaki Y, Takahashi Y, No shinkei geka. Neurological surgery, 2013, vol. 41, no. 9, pp. 765-771

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  • Initial experience of a novel sheath guide for transbrachial carotid artery stenting: technical note. Reviewed International journal

    Iwata T, Mori T, Miyazaki Y, Nakazaki M, Takahashi Y, Mizokami K

    Journal of neurointerventional surgery   5 Suppl 1   i77 - 80   2013.5

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    Iwata T, Mori T, Miyazaki Y, Nakazaki M, Takahashi Y, Mizokami K, Journal of neurointerventional surgery, 2013, vol. 5 Suppl 1, pp. i77-80

    DOI： 10.1136/neurintsurg-2012-010506

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  • Initial Experience of a Novel Sheath Guide for Transbrachial Coil Embolization of Cerebral Aneurysms in the Anterior Cerebral Circulation Reviewed International journal

    Tomonori Iwata, Takahisa Mori, Hiroyuki Tajiri, Yuichi Miyazaki, Masahito Nakazaki, Koji Mizokami

    Operative Neurosurgery   72 ( 1 Suppl Operative )   ons 15 - ons 20   2013.3

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    BACKGROUND: The transfemoral approach is a common technique for coil embolization of cerebral aneurysms in the anterior cerebral circulation. However, it is difficult to advance a guiding catheter into the carotid artery via the femoral route in patients with a tortuous aortic arch, an unfavorable supra-aortic takeoff, aortic diseases, or occlusion of the femoral artery. OBJECTIVE: To report our initial experiences of coil embolization of cerebral aneurysms in the anterior cerebral circulation with a novel sheath guide for transbrachial carotid cannulation. METHODS: A sheath guide designed specifically for transbrachial carotid cannulation was developed; transbrachial coil embolization for cerebral aneurysms began in May 2011. Included for analysis were patients who underwent transbrachial coil embolization for cerebral aneurysms in the anterior cerebral circulation from May 2011 to January 2012. Adjuvant techniques, angiographic results, procedural success, and periprocedural complications were investigated. RESULTS: Ten patients underwent transbrachial coil embolization of cerebral aneurysms in the anterior cerebral circulation. All procedures were successful using the brachial route. No periprocedural complications occurred. Patients were permitted to get seated immediately after coil embolization even during hemostasis. CONCLUSION: The sheath guide specifically designed for transbrachial carotid cannulation was useful for coil embolization of cerebral aneurysms in the anterior cerebral circulation.

    DOI： 10.1227/neu.0b013e31826e2cd9

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  • Safety and effectiveness of emergency carotid artery stenting for a high-grade carotid stenosis with intraluminal thrombus under proximal flow control in hyperacute and acute stroke. Reviewed International journal

    Iwata T, Mori T, Tajiri H, Miyazaki Y, Nakazaki M

    JOURNAL OF NEUROINTERVENTIONAL SURGERY   5 ( 1 )   40 - 44   2013.1

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    DOI： 10.1136/neurintsurg-2011-010147

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  • Repeated Injection of Contrast Medium Inducing Dysfunction of the Blood-Brain Barrier Reviewed

    Tomonori IWATA, Takahisa MORI, Hiroyuki TAJIRI, Yuichi MIYAZAKI, Masahito NAKAZAKI

    Neurol. Med. Chir.(Tokyo)   53 ( 1 )   34 - 36   2013

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    An early 60s-year-old man suffered reversible dysfunction of the blood-brain barrier (BBB) induced by repeated injection of contrast medium during coil embolization of intracranial unruptured aneurysm. He presented with convulsion during coil embolization, and neurological symptoms of aphasia and right hemiparesis continued for 5 days, and then improved completely. All transient radiological abnormalities were limited to the territory of the left internal carotid artery, where contrast medium was injected repeatedly. Repeated computed tomography, magnetic resonance imaging, single-photon emission computed tomography, and cerebrospinal fluid test findings indicated that temporary dysfunction of the BBB might have occurred. Dysfunction of the BBB in the anterior circulation induced by contrast medium is rare. Tolerance to toxicity of contrast medium may depend on the individual patient, and repeated injection of contrast medium may cause dysfunction of the BBB, leading to toxic dysfunction directly in the brain.

    DOI： 10.2176/nmc.53.34

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  • Long-term Angiographic and Clinical Outcome Following Stenting by Flow Reversal Technique for Chronic Occlusions Older Than 3 Months of the Cervical Carotid or Vertebral Artery Reviewed

    Tomonori Iwata, Takahisa Mori, Hiroyuki Tajiri, Yuichi Miyazaki, Masahito Nakazaki

    NEUROSURGERY   70 ( 1 )   82 - 90   2012.1

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    DOI： 10.1227/NEU.0b013e31822e074c

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  • Predictors of Hyperperfusion Syndrome Before and Immediately After Carotid Artery Stenting in Single-Photon Emission Computed Tomography and Transcranial Color-Coded Real-Time Sonography Studies Reviewed

    Tomonori Iwata, Takahisa Mori, Hiroyuki Tajiri, Masahito Nakazaki

    Neurosurgery   68 ( 3 )   649 - 656   2011.3

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    DOI： 10.1227/neu.0b013e3182077ed8

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  • Short-term clinical outcome following gastrointestinal tube feeding of immunonutrition-oriented (IMPACT®) or protein-oriented food (PEMVest®) in acute stroke management Reviewed

    Hiroyuki Tajiri, Takahisa Mori, Tomonori Iwata, Yuichi Miyazaki, Masahito Nakazaki

    Jpn. J. Stroke   33 ( 3 )   305 - 312   2011

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    DOI： 10.3995/jstroke.33.305

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  • SUCCESSFUL STENTING BY COMBINATION TECHNIQUE OF REVERSE FLOW AND DOWNSTREAM FILTERING FOR LONG CHRONIC TOTAL OCCLUSION OF THE CERVICAL VERTEBRAL ARTERY Reviewed

    Tomonori Iwata, Takahisa Mori, Hiroyuki Tajiri, Masahito Nakazaki

    Neurosurgery   65 ( 2 )   E378 - E379   2009.8

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    DOI： 10.1227/01.neu.0000348293.01482.0f

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  • 脳梗塞に対する血栓回収療法後の骨髄間葉系幹細胞による細胞治療

    中崎公仁, 佐々木祐典, 佐々木祐典, 佐々木優子, 岡真一, 浪岡隆洋, 浪岡愛, KOCSIS Jeffery, 本望修, 本望修

    脳血管内治療(Web)   1 ( Supplement )   S221(J‐STAGE) - S221   2016.11

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  • Regenerative therapy using autologous mesenchymal stem cell for cerebral ischemia

    13 ( 3 )   304 - 308   2014.8

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  • Preservation of interhemispheric cortical connections through corpus callosum following intravenous infusion of mesenchymal stem cells in a rat model of cerebral infarction. Reviewed International journal

    Nagahama H, Nakazaki M, Sasaki M, Kataoka-Sasaki Y, Namioka T, Namioka A, Oka S, Onodera R, Suzuki J, Sasaki Y, Kocsis JD, Honmou O

    Brain research   1695   37 - 44   2018.5

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    DOI： 10.1016/j.brainres.2018.05.033

    ORCID Put Code : 49547017

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  • T1 Black Blood imagingによる椎骨動脈解離の経時的変化(Temporal Change of Signal Intensity of Intramural Hematoma in Patients with Acute Vertebral Artery Dissection Using T1-Weighted Black Blood Imaging)

    本田 修, 中崎 公仁, 佐々木 祐典, 野中 雅, 高橋 明, 橋本 祐治, 米増 保之, 野村 達史, 恩田 敏之, 大坊 雅彦

    CI研究   39 ( 2 )   71 - 77   2017.11

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  • 脳小血管病と急性再開通治療3ヵ月後の臨床転帰との関係

    中崎 公仁, 野中 雅, 野村 達史, 恩田 敏之, 米増 保之, 高橋 明, 橋本 祐治, 本田 修, 佐々木 祐典, 大坊 雅彦, 本望 修

    脳血管内治療   2 ( Suppl. )   S170 - S170   2017.11

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  • 脳小血管病と緊急血栓回収療法の臨床転帰との関係

    中崎公仁, 野中雅, 野村達史, 恩田敏之, 野中雅, 野村達史, 恩田敏之, 米増保之, 高橋明, 橋本祐治, 本田修, 佐々木祐典, 大坊雅彦, 本望修

    脳循環代謝(Web)   29 ( 1 )   159 - 159   2017.11

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  • 慢性期脊髄損傷動物モデルに対する骨髄間葉系幹細胞の経静脈的投与による機能回復の検討

    森田智慶, 佐々木祐典, 佐々木優子, 中崎公仁, 長濱宏史, 岡真一, 押切勉, 吉本三徳, 本望修, 山下敏彦

    日本整形外科学会雑誌   91 ( 8 )   S1677 - S1677   2017.8

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  • 脊髄損傷の病態と再生 慢性期脊髄損傷動物モデルに対する骨髄間葉系幹細胞の経静脈的投与による機能回復の検討

    森田 智慶, 佐々木 祐典, 佐々木 優子, 中崎 公仁, 長濱 宏史, 岡 真一, 押切 勉, 吉本 三徳, 本望 修, 山下 敏彦

    日本整形外科学会雑誌   91 ( 8 )   S1677 - S1677   2017.8

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  • Therapeutic effect by combining rehabilitation and intravenous infusion of mesenchymal stem cells after experimental stroke in rats

    佐々木雄一, 佐々木雄一, 佐々木雄一, 佐々木雄一, 佐々木祐典, 佐々木祐典, 佐々木優子, 佐々木優子, 中崎公仁, 中崎公仁, 岡真一, 岡真一, 浪岡隆洋, 浪岡隆洋, 浪岡愛, 浪岡愛, 柿澤雅史, 本望修, 本望修

    脳循環代謝(Web)   28 ( 2 )   281‐289(J‐STAGE) - 289   2017.8

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    DOI： 10.16977/cbfm.28.2_281

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  • ラット慢性期脊髄損傷モデルに対する骨髄間葉系幹細胞の経静脈的投与による機能回復の検討

    森田 智慶, 佐々木 祐典, 佐々木 優子, 中崎 公仁, 岡 真一, 押切 勉, 竹林 庸雄, 本望 修, 山下 敏彦

    移植   51 ( 6 )   518 - 518   2016.12

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  • 脳小血管病と急性再開通治療3ヶ月後の臨床転帰との関係

    中崎公仁, 野中雅, 野中雅, 高橋明, 米増保之, 野村達史, 野村達史, 恩田敏之, 恩田敏之, 本田修, 橋本祐治, 佐々木祐典, 本望修

    脳血管内治療(Web)   1 ( Supplement )   S115(J‐STAGE) - S115   2016.11

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  • CT perfusionによる急性期主幹動脈閉塞症例のischemic core/penumbra予測

    恩田敏之, 中崎公仁, 野村達史, 米増保之, 橋本祐治, 本田修, 高橋明, 野中雅, 大坊雅彦

    脳血管内治療(Web)   1 ( Supplement )   S65(J‐STAGE) - S65   2016.11

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  • 脳梗塞患者に対する骨髄間葉系幹細胞移植後の経時的身体機能変化

    佐々木雄一, 佐々木雄一, 佐々木祐典, 岡真一, 中崎公仁, 佐々木優子, 浪岡隆洋, 浪岡愛, 小野寺理恵, 奥山航平, 山下達郎, 柿澤雅史, 石合純夫, 本望修

    日本理学療法学術大会(Web)   51st ( Suppl.2 )   P‐NV‐11‐4(J‐STAGE) - NV   2016.10

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    DOI： 10.14900/cjpt.2015.1063

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  • 脳梗塞患者に対する骨髄間葉系幹細胞移植後の経時的身体機能変化

    佐々木 雄一, 佐々木 祐典, 岡 真一, 中崎 公仁, 佐々木 優子, 浪岡 隆洋, 浪岡 愛, 小野寺 理恵, 奥山 航平, 山下 達郎, 柿澤 雅史, 石合 純夫, 本望 修

    理学療法学   43 ( Suppl.2 )   P - NV   2016.10

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    DOI： 10.14900/cjpt.2015.1063

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  • 脊髄損傷患者に対する自家培養骨髄間葉系幹細胞の静脈内投与―医師主導治験(Phase 2)―

    押切勉, 押切勉, 竹林庸雄, 吉本三雄, 寺島嘉紀, 嘉野真允, 森田智慶, 森田智慶, 山下敏彦, 佐々木祐典, 岡真一, 中崎公仁, 佐々木優子, 浪岡隆洋, 浪岡愛, 本望修

    Journal of Spine Research   7 ( 3 )   574   2016.3

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  • rt‐PA静注後の出血性梗塞に対する骨髄間葉系幹細胞の抑制効果

    中崎公仁, 佐々木祐典, 佐々木優子, 岡真一, 浪岡隆洋, 浪岡愛, 本望修

    脳循環代謝(Web)   28 ( 1 )   194(J‐STAGE)   2016

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  • 実験的脳梗塞に対する骨髄間葉系幹細胞移植とリハビリテーションの相乗効果

    佐々木雄一, 佐々木雄一, 佐々木雄一, 佐々木雄一, 佐々木祐典, 佐々木祐典, 佐々木優子, 佐々木優子, 中崎公仁, 中崎公仁, 岡真一, 岡真一, 浪岡隆洋, 浪岡隆洋, 浪岡愛, 浪岡愛, 柿澤雅史, 石合純夫, 石合純夫, 本望修, 本望修

    脳循環代謝(Web)   28 ( 1 )   193(J‐STAGE)   2016

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  • Regenerative medicine for cerebral infarction

    42 ( 5 )   409 - 413   2014.5

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  • 神経保護と神経再生 ラット脳梗塞モデルに対する骨髄間葉系幹細胞移植後のfMRIによる皮質賦活信号と運動機能改善との関連性

    中崎 公仁, 鈴木 淳平, 小野寺 理恵, 佐々木 優子, 岡 真一, 佐々木 祐典, 本望 修

    脳循環代謝   25 ( 1 )   108 - 108   2013.11

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  • 脳低温療法を更に普及するための展望 再生医療 心肺停止後全脳虚血に対する骨髄幹細胞の静脈内投与による治療法の検討

    佐々木 祐典, 小野寺 理恵, 岡 真一, 佐々木 優子, 中崎 公仁, 中村 秀之, 山崎 弥生, 須永 隆文, 泉 佳代子, 本望 修

    日本脳低温療法学会プログラム・抄録集   16回   41 - 41   2013.7

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    Language：Japanese   Publisher：日本脳低温療法・体温管理学会  

    Ichushi

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  • Simple And Easy Way Using Time-Intensity Curve of Perfusion-Weighted Images to Find Penumbra In Stroke Patients Within 4.5 Hours Of Onset Due To The Carotid Artery Occlusion

    Takahisa Mori, Tomonori Iwata, Yuichi Miyazaki, Masahito Nakazaki, Yoichiro Takahashi, Koji Mizokami

    STROKE   44 ( 2 )   2013.2

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  • The Appropriate Body Position During Nasal-gastric Tube Feeding To Prevent The Aspiration Pneumonia In Acute Stroke Patients

    Haruka Suzuki, Sayaka Takeda, Masahito Nakazaki, Sachiko Sone, Takahisa Mori

    STROKE   44 ( 2 )   2013.2

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  • Blood Sampling Oxygen Extraction Fraction As Predictors Of Hyperperfusion Phenomenon Following Carotid Artery Stenting

    Tomonori Iwata, Takahisa Mori, Yuichi Miyazaki, Masahito Nakazaki, Yoichiro Takahashi, Koji Mizokami

    STROKE   44 ( 2 )   2013.2

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  • The usefulness of time intensity curve generated from MRI/PWI to predict neurological deterioration after onset in acute ischemic stroke patients

    M. Nakazaki, T. Mori, H. Tajiri, T. Iwata, Y. Miyazaki, K. Mizogami

    EUROPEAN JOURNAL OF NEUROLOGY   19   156 - 156   2012.9

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  • Long-term Angiographic and Clinical Outcome Following Stenting by Flow Reversal Technique for Chronic Occlusions Older Than 3 Months of the Cervical Carotid or Vertebral Artery Reviewed International journal

    Tomonori Iwata, Takahisa Mori, Hiroyuki Tajiri, Yuichi Miyazaki, Masahito Nakazaki

    Neurosurgery   70 ( 1 )   82 - 90   2012.1

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    Language：English   Publisher：Ovid Technologies (Wolters Kluwer Health)  

    DOI： 10.1227/neu.0b013e31822e074c

    ORCID Put Code : 23107581

    PubMed

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  • Subacute Angioplasty And/or Stenting For The Stroke Patients Deteriorating Due To Vertebrobasilar Stenosis

    Tomonori Iwata, Takahisa Mori, Hiroyuki Tajiri, Yuichi Miyazaki, Masahito Nakazaki

    STROKE   42 ( 3 )   E323 - E323   2011.3

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  • Predictors of Hyperperfusion Syndrome Before and Immediately After Carotid Artery Stenting in Single-Photon Emission Computed Tomography and Transcranial Color-Coded Real-Time Sonography Studies International journal

    Tomonori Iwata, Takahisa Mori, Hiroyuki Tajiri, Masahito Nakazaki

    NEUROSURGERY   68 ( 3 )   649 - 655   2011.3

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  • The Usefulness Of DWI-aspect Score As A Predictor Of Short And Long-term Clinical Outcome Following Emergency Reperfusion Therapy In Severe Acute Ischemic Stroke Patients

    Masahito Nakazaki, Takahisa Mori, Hiroyuki Tajiri, Tomonori Iwata, Yuichi Miyazaki

    STROKE   42 ( 3 )   E317 - E317   2011.3

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  • Long-term Angiographic Follow-up Following Stenting For Chronic Total Occlusion Older Than Three Months Of The Proximal Subclavian Artery

    Yuichi Miyazaki, Takahisa Mori, Hiroyuki Tajiri, Tomonori Iwata, Masahito Nakazaki

    STROKE   42 ( 3 )   E236 - E236   2011.3

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  • Angioplasty and Stenting for the Internal Carotid or Middle Cerebral Artery Occlusion in a Subacute Stroke Stage in Deteriorating Patients With Internal Border Zone Infarcts

    Tomonori Iwata, Takahisa Mori, Hiroyuki Tajiri, Tsuyoshi Uesugi, Masahito Nakazaki

    STROKE   41 ( 4 )   E355 - E355   2010.4

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  • Long-term angiographic and clinical outcomes following stenting by proximal flow control technique for chronic total occlusions of the cervical carotid and vertebral arteries

    T. Iwata, T. Mori, H. Tajiri, M. Nakazaki

    EUROPEAN JOURNAL OF NEUROLOGY   16   396 - 396   2009.10

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  • Predictive factors of hyper-perfusion syndrome before and immediately after carotid artery stenting: diagnostic utility of single-photon emission computed tomography and transcranial colour-coded real-time sonography study

    T. Iwata, T. Mori, H. Tajiri, M. Nakazaki

    EUROPEAN JOURNAL OF NEUROLOGY   16   115 - 115   2009.10

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  • Predictive factors of cerebral hyperperfusion syndrome before and immediately after carotid angioplasty and stent placement

    T. Iwata, T. Mori, H. Tajiri, M. Nakazaki

    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM   29   S112 - S113   2009.10

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  • The effectiveness of the teleconsultation system using mobile picture mail phones on clinical outcome of acute stroke patients

    M. Nakazaki, T. Mori, H. Tajiri, T. Iwata

    EUROPEAN JOURNAL OF NEUROLOGY   16   402 - 402   2009.10

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  • The most important predictor of 3-month clinical outcome after appropriate treatment based on emergency MRI and intensive rehabilitation for symptomatic hyperacute ischemic stroke

    M. Nakazaki, T. Mori, H. Tajiri, T. Iwata, T. Imanishi, H. Tanaka, T. Inoue, H. Seki

    EUROPEAN JOURNAL OF NEUROLOGY   16   402 - 402   2009.10

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  • SUCCESSFUL STENTING BY COMBINATION TECHNIQUE OF REVERSE FLOW AND DOWNSTREAM FILTERING FOR LONG CHRONIC TOTAL OCCLUSION OF THE CERVICAL VERTEBRAL ARTERY: TECHNICAL CASE REPORT International journal

    Tomonori Iwata, Takahisa Mori, Hiroyuki Tajiri, Masahito Nakazaki

    NEUROSURGERY   65 ( 2 )   378 - 379   2009.8

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  • Predictive factors of cerebral hyperperfusion syndrome before and immediately after carotid angioplasty and stent placement: diagnostic utility of single-photon emission computed tomography and transcranial colour-coded real-time sonography study

    T. Iwata, T. Mori, H. Tajiri, M. Nakazaki

    JOURNAL OF NEUROLOGY   256   S38 - S39   2009.6

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  • Long-term angiographic and clinical outcomes following stenting under flow reversal by proximal flow control technique for chronic total occlusions of the cervical carotid and vertebral arteries

    T. Iwata, T. Mori, H. Tajiri, M. Nakazaki

    JOURNAL OF NEUROLOGY   256   S212 - S212   2009.6

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Presentations

  • 米国神経外傷学会 (Neurotrauma) Plenary session 招待講演 Invited

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    Presentation type：Symposium, workshop panel (nominated)  

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  • Systemic administration of mesenchymal stem cells inhibits reperfusion injury following intravenous rt-PA therapy for transient middle cerebral artery occlusion in rats Invited

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    Presentation type：Symposium, workshop panel (public)  

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Industrial property rights

  • 脳梗塞の治療用医薬

    本望 修, 中崎 公仁, 佐々木 祐典, 佐々木 優子, 岡 真一

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    Applicant：北海道公立大学法人 札幌医科大学, ニプロ株式会社

    Application no：特願2015-254410  Date applied：2015.12

    Announcement no：特開2017-114827  Date announced：2017.6

    J-GLOBAL

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  • 寿命延長剤

    本望 修, 佐々木 祐典, 佐々木 優子, 前澤理恵, 岡 真一, 中崎 公仁

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    Application no：特願2018-534267 

    Announcement no：特開WO2018/034023 

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  • ステント内再狭窄の予防のための医薬組成物

    本望 修, 佐々木 祐典, 佐々木 優子, 前澤理恵, 岡 真一, 中崎 公仁

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    Application no：特願2020-571280 

    Announcement no：特開WO2020/162580 

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  • 筋萎縮性側索硬化症の治療用医薬組成物

    本望 修, 佐々木 祐典, 佐々木 優子, 前澤理恵, 岡 真一, 中崎 公仁

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    Application no：特願2021-505167 

    Announcement no：特開WO2020/184729 

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  • シナプス形成剤

    本望 修, 佐々木 祐典, 佐々木 優子, 前澤理恵, 岡 真一, 中崎 公仁

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    Application no：特願2022-101637 

    Announcement no：特開特開2022-126812 

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Awards

  • 日本細胞外小胞学会学術集会奨励賞

    2024.10  

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  • 日本脳卒中学会 最優秀口演賞

    2018.3  

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  • 上原財団海外留学助成 リサーチフェローシップ

    2018.3  

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  • ヨーロッパ脳卒中学会 Young Investigator Award

    2009.5  

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  • 日本脳卒中学会 優秀ポスター賞

    2013.3  

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Research Projects

  • Amplification Mechanisms of Neuroprotective and Neurotrophic Effects Mediated by Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles

    Grant number：25K12482  2025.4 - 2028.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • Restoration of cognitive impairment following intravenous infusion of mesenchymal stem cells in a rat model of cerebral small vessel disease

    Grant number：15K10312  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Nakazaki Masahito, HONMOU Osamu

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    Recently, intravenous mesenchymal stem cells (MSC) transplantation has been reported that greater therapeutic efficacy can be achieved via multiple mechanisms for various disorders. In this study, we aimed to investigate the effect of MSC transplantation in a rat model of vascular dementia by histological, MRI, and behavioral analysis. We used the Spontaneously hypertensive rats stroke-prone (SHRSP) with cognitive impairment. At week 21of age, transplantation of MSC was performed by intravenous injection. Compared with the vehicle group, the MSC infused group showed a significant improvement in cognitive function. The MRI demonstrated that the MSC infused group showed a significant reduction of brain atrophy compared to the vehicle group. The histological analysis also showed the volume of cerebral cortex and hippocampus were higher in MSC group than vehicle group. Collectively, intravenous infusion of MSCs might provide therapeutic efficacy in a rat model of vascular dementia.

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  • Mechanistic Analysis of Neural plasticity by Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells

    Grant number：25K12509  2025.4 - 2028.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • Optimization of Mesenchymal Stem Cell Therapy for Spinal Cord Injury.

    Grant number：25K12366  2025.4 - 2028.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • 脳梗塞に対するsmall Extracellular Vesicles静脈投与療法の治療メカニズムの解明

    Grant number：25K12323  2025.4 - 2028.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    鵜飼 亮, 佐々木 祐典, 横山 貴裕, 中崎 公仁, 本望 修

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • 骨髄間葉系幹細胞由来細胞外小胞による脊髄損傷治療の最適化

    2024.9 - 2025.3

    公益財団法人北海道科学技術総合振興センター  札幌バイオシーズ事業化支援事業（札幌バイオシーズ事業化支援補助金） 

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    Authorship：Principal investigator 

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  • 脊髄損傷に対する骨髄間葉系幹細胞移植による、脳脊髄の可塑性亢進メカニズムの解析

    Grant number：24K12269  2024.4 - 2027.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    岡 真一, 鵜飼 亮, 横山 貴裕, 中崎 公仁

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • 脳梗塞に対する骨髄幹細胞治療による神経回路の再構築の革新的MRIによる統合的解析

    Grant number：24K12246  2024.4 - 2027.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    長濱 宏史, 佐々木 祐典, 本望 修, 中崎 公仁

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • 慢性期脳梗塞に対する骨髄幹細胞治療における至適リハビリ条件の探索

    Grant number：24K14250  2024.4 - 2027.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    山下 達郎, 佐々木 雄一, 佐々木 祐典, 鵜飼 亮, 岡 真一, 佐々木 優子, 本望 修, 中崎 公仁

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • Therapeutic strategies for cerebral infarction and spinal cord injury by activating plasticity throughout the central nervous system

    Grant number：23K24447  2024.4 - 2025.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount：\5460000 （ Direct Cost: \4200000 、 Indirect Cost：\1260000 ）

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  • Intravenous infusion of mesenchymal stem cells enhance plasticity in the brain of rat model of experimental spinal cord injury

    Grant number：18K09071  2018.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Nagahama Hiroshi

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    Grant amount：\3900000 （ Direct Cost: \3000000 、 Indirect Cost：\900000 ）

    The enhanced neural plasticity at the injured tissue and/or in the higher level of spinal cord and brain following intravenous infusion of MSCs in spinal cord injury (SCI) model was thought to be due to protection from neuronal, axonal loss or degeneration in the injured tissue, and stabilization of the blood-spinal cord barrier. Furthermore, we analyzed the variable genes expressed in the motor cortex at the 3 days post-MSC infusion, when functional improvement was observed, and found that there were changes in the expression levels of several genes, which may enhance neural plasticity. Consequently, we found that intravenous infusion of MSCs in SCI may promote the functional improvement through the enhanced neural plasticity induced at the injured tissue and at the upper spinal cord and brain.

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  • Analysis of accelerating plasticity in the brain following intravenous infusion of mesenchymal stem cells in spinal injury

    Grant number：18K08975  2018.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    OKA SHINICHI

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    Neurofunctional recovery in spinal cord injury following intravenous infusion of Mesenchymal stem cells has been reported. It is one of the most important mechanisms of functional improvement that remote responses occur in the brain as well as in the injured spinal cord. Therefore, we performed MRI analysis after MSC administration for spinal cord injury in patients and animal experimental models, and histological analysis for animal models at the same time, and clarified that neural circuit rearrangement occurred.

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  • Analysis of the neural circuits reconstructed by interneurons in mesenchmal stem cell transplantation for spinal cord injury

    Grant number：18K09072  2018.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Hirota Ryosuke

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    The reorganization of neural circuits in the brain after spinal cord injury has been previously reported using MRI diffusion tensor imaging and other techniques, but there are few reports using detailed neuroanatomical methods. The purpose of this study was to analyze in detail the reorganization of neural circuits in the brain after spinal cord injury using adeno-associated virus (AAV), which is known as a progressive neural tracer.
    AAV-8 carrying the CAG promoter was found to have high efficiency of transduction, adaptive tracking, and cell-selective labeling in the brain. Furthermore, analysis of the brain after spinal cord injury using the same vector suggested that neural circuit reconstruction had occurred.

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  • Functional recovery following intravenous infusion of mesenchymal stem cells via induction of neural plasticity in chronic spinal cord injury

    Grant number：17K10902  2017.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Morita Tomonori

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    Intravenous infusion of mesenchymal stem cells (MSCs) has been shown to provide functional improvements in spinal cord injury (SCI) through local therapeutic mechanisms that provide neuroprotection, remyelination, and axonal sprouting. Recent evidence has demonstrated that remote responses in the brain, as well as local responses in the injured spinal cord, can be induced after SCI. In the present study, we examined the brain response that might be associated with the functional improvements induced by the infused MSCs after SCI. Genome-wide RNA profiling was performed in the motor cortex of SCI rats at 3 days post-MSC or vehicle infusion. Then, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) data revealed that the seven behaviorally-associated differentially expressed genes (DEGs) had significant correlations with the behavioral function. These behaviorally-associated DEGs may be related to the functional recovery after systemic infusion of MSCs in SCI.

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  • Improvement in neural function following intravenous infusion of mesenchymal stem cells in experimental cerebral stroke

    Grant number：17K10901  2017.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Suzuki Junpei

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    Intravenous of mesenchymal stem cells (MSCs) following cerebral infarction exerts functional recovery. Previous study has suggested potential therapeutic mechanisms that promote neuroprotection and synaptogenesis, secretion of neurotrophic factors, remodeling of neural circuits, and elevation of trophic factors. In addition to these mechanisms, we hypothesized that restored interhemispheric connectivity might be an additional mechanism of neural improvements. In this study, we have demonstrated that there was anatomical restoration of cortical interhemispheric connections after infused MSCs in middle cerebral artery occlusion (MCAO). These results suggest that distinct preservation of interhemispheric cortical connections through corpus callosum was preserved by intravenous infusion of MSCs. This anatomical preservation of the motor cortex in the contralateral hemisphere may contribute to improvements in neural function after MSC therapy for cerebral stroke.

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  • analysis of molecular mechanism of invasion in malignant gliomas and development of a novel treatment by inhibition of glioma cell migrations

    Grant number：17K10872  2017.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Wanibuchi Masahiko

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    Gliomas account for 24.1% of primary brain tumors. It is difficult to cure the disease with multimodality treatment combined with surgery, chemotherapy, and radiotherapy. The 5-year survival rate of glioblastoma which is the most malignant type of gliomas is only 10.1%. The reason for the poor prognosis is the invasive capacity, however, the factors and mechanisms of invasion or migration is still unknown.In this study, we found several factors which related to the prognosis of gliomas such as ACTC1 (actin alpha cardiac muscle 1), SERPINEA1, IL13 receptor alpha 2. Among these, ACTC1 was also closely related to the invasion of malignant gliomas. In addition, timelapse study of U87 malignant glioma cell line revealed gene knockdown of ACTC1 using by siRNA resulted in the inhibition of migration of glioma cells. The present study demonstrated that targeting of migration capacity of glioma cells may lead to the improvement of prognosis of malignant gliomas.

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  • Functional recovery following intravenous infusion of mesenchymal stem cells in experimental spinal cord injury

    Grant number：16K10794  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Sasaki Masanori

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    Recent studies has demonstrated that remote responses in the brain, as well as local responses in the injured spinal cord, can be occurred following spinal cord injury (SCI). Intravenous infusion of mesenchymal stem cells (MSCs) has been shown to elicit functional recovery in SCI through local mechanisms. We studied brain response that might be associated with the functional improvements induced by the infused MSCs following SCI. Genomewide RNA profiling was conducted in the motor cortex of SCI rats at 3 days post infusion. Then, qRT-PCR revealed that the ‘‘behaviorally-associated differentially expressed genes (DEGs)’’ were identified by the Pearson’s correlation analysis with the behavioral function, suggesting that these genes may be related to the functional recovery after infused MSCs. These results suggested that the infused MSCs alter the gene expression signature in the brain and that these expression changes may contribute to the improved function.

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  • Prevention of neointimal hyperplasia induced by an endovascular stent via intravenous infusion of mesenchymal stem cells

    Grant number：16K10731  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Katsuya Komatsu

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    In-stent restenosis causes recurrent ischemic events. Neointimal hyperplasia induced by an inflammatory response to the stent strut may be a possible mechanism of in-stent restenosis. Intravenous infusion of mesenchymal stem cells (MSCs) has been reported to show therapeutic efficacy for cerebral stroke presumably by an anti-inflammatory effect. This study aimed to determine whether MSCs can reduce or prevent neointimal hyperplasia induced by an endovascular stent. We deployed two types of stents using an animal model. Stents were implanted in the common carotid artery (CCA), and superficial cervical artery (SCA). Infused MSC immediately after deployment of stents prevented in-stent stenosis of CCA and SCA. Intravenous infusion of MSCs inhibited the inflammatory reaction to an implanted stent strut, and prevented progressive neointimal hyperplasia in the stented CCA and SCA. Thus, MSC treatment could attenuate the recurrence of cerebral ischemic events after stenting.

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  • Development of new therapy with mesenchymal stem cell for reperfusion injury following reperfusion therapy

    Grant number：16K10730  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Honmou Osamu

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    Reperfusion therapy with rtPA is the standard therapy for stroke. However, hemorrhagic complications can result. Intravenous infusion of MSCs provides therapeutic efficacy. One suggested mechanism is inhibition of endothelial dysfunction. Four groups were studied: 1) NS+vehicle, 2) rtPA+vehicle, 3) NS+MSCs, 4) rtPA+MSCs. The MSC-treated groups (3,4) experienced a greater reduction in the incidence rate of intracerebral hemorrhage and hemorrhagic volume after tMCAO even if rtPA was received. Behavioral testing indicated that MSC-infused groups had greater improvement, but rtPA+MSCs provided greater improvement than MSCs alone. The rCBF ratio of rtPA groups (2,4) was similar at 2 hours after reperfusion of tMCAO, but both were greater than that in non-rtPA groups. Infused MSCs may inhibit endothelial dysfunction to suppress hemorrhagic events and facilitate functional outcome. Combined therapy MSCs and rtPA facilitated early behavioral recovery.

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  • Analysis of neural plasticity induced by intravenous infusion of mesenchymal stem cells in experimental model of cerebral infarction

    Grant number：15K10365  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Hiroshi Nagahama

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    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    Intravenous infusion of mesenchymal stem cells (MSCs) improves behavioral function in rat stroke models. MRI Diffusion tensor imaging tractography demonstrated that increasedmore “number of tracks” was observed in the MSC-treated group compared to the non-treated group. The number of synaptic puncta in non-infarcted the cortex in the MSC-treated group was higher than the non-treated group. Corpus callosum thickness was greater in the MSC-treated group than the non-treated group. These results suggested enhanced plasticity was occurred following intravenous infusion of MSCs in cerebral infarction. It is conceivable that these processmechanisms might contribute to functional improvement by the infused MSCs in strokefrom cerebral infarction.

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  • INTRAVENOUS INFUSION OF MESENCHYMAL STEM CELLS PROMOTES FUNCTIONAL RECOVERY IN A MODEL OF CHRONIC SPINAL CORD INJURY

    Grant number：26462213  2014.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Morita Tomonori, HONMOU Osamu

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    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    Intravenous infusion of mesenchymal stem cells (MSCs) derived from bone marrow improves behavioral function in rat models of acute spinal cord injury (SCI). In this study, MSCs were infused 10 weeks after the induction of a severe contusive SCI. Locomotor function was assessed until 20 weeks post-SCI. Motor recovery was greater in the MSC group with rapid improvement beginning in earlier post-infusion times than in the vehicle group. Blood spinal cord barrier (BSCB) integrity was assessed by the intravenous infusion of Evans Blue with quantitation of its leakage, and that was reduced in the MSC group. There was extensive remyelination around the lesion center and increased neovascularization/sprouting of the nerve fibers. These results indicate that the MSC therapy results in functional improvements that is associated with structural changes in the chronically injured spinal cord including stabilization of the BSCB, axonal sprouting/regeneration and remyelination.

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  • Therapeutic Effects of Intravenous Infusion of MSCs in Hypoxic-Ischemic Encephalopathy Rat

    Grant number：26462168  2014.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Sakai Takuro, HONMOU Osamu

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    We aimed to investigate the effect of mesenchymal stem cells (MSCs) transplantation in a rat model of neonatal hypoxic-ischemic encephalopathy (HIE) by histological, MRI, and behavioral analysis. At postnatal day 7, rats were underwent HI by left common carotid artery occlusion followed by 120 min hypoxia (8% oxygen). At postnatal day 10, transplantation of MSCs was performed by intravenous injection. Compared with the vehicle (control) group, the MSC infused group showed a significant improvement in athletic performance by the evaluation with the beam walk test. The MRI also demonstrated that the MSC infused group showed a significant reduction of the ischemic volume compared to the vehicle group. Collectively, intravenous infusion of MSCs might provide therapeutic efficacy in a rat model of HIE.

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  • Induced neural plasticity by intravenous infusion of mesenchymal stem cells (MSC) and rehabilitation in ischemic brain

    Grant number：26350618  2014.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Sasaki Yuichi

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    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat stroke models. The purpose of this study was to investigate whether synergic effects of daily rehabilitation and intravenous infusion of MSCs has therapeutic effects after stroke in rats. A permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament. Rat MSCs were intravenously infused after MCAO induction, and the rats received daily rehabilitation with treadmill running exercise. Both combined therapy and MSC infusion reduced lesion volume, induced synaptogenesis, and elicited functional improvement compared with the groups without MSC infusion, but the effect was greater in the combined therapy group. The data indicate that the combined therapy of daily rehabilitation and intravenous infusion of MSCs improved functional outcome in a rat MCAO model.

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  • Fundamental analysis of ischemic brain plasticity induced by bone marrow mesenchymal stem cell transplantation

    Grant number：26462214  2014.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Suzuki Junpei

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    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    Intravenous infusion of mesenchymal stem cells (MSCs) from adult bone marrow ameliorates functional deficits in rat cerebral infarction models. In this study, we found functional improvements evaluated with behavioral testing following systemic administration of MSCs in stroke. Immunohistochemical analysis demonstrated that synaptogenesis was induced around the ischemic lesion in the MSC treated group. Collectively, neural plasticity might contribute to the functional recovery following intravenous infusion of MSCs in a rat model of stroke.

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  • Functional recovery following intravenous infusion of MSCs via repair of pericytes in rat spinal cord injury

    Grant number：25462227  2013.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Sasaki Masanori, Wanibuchi Masahiko, Mikami Takeshi, Kobayashi Masaki, Nakazaki Masahito, Sakai Takuro, Sasaki Yuichi, Suzuki Junpei, Morita Tomonori, Namioka Ai, Namioka Takahiro

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    Grant amount：\5070000 （ Direct Cost: \3900000 、 Indirect Cost：\1170000 ）

    Mesenchymal stem cells (MSCs) derived from bone marrow may represent a potential source for organ regeneration via multiple mechanisms based on animal experiments. In this study, we induced a contusive SCI at T9 in the rat and studied the effects of intravenous MSC infusion on blood spinal cord barrier (BSCB) permeability, microvascular architecture and locomotor recover. Spatial and temporal changes in BSCB integrity were assessed by intravenous infusions of Evans blue (EvB). SCI resulted in prolonged BSCB leakage that was most severe at the impact site but disseminated extensively rostral and caudal to the lesion. Contused spinal cords also showed an increase in microvasculature. In MSC-treated rats, BSCB leakage was reduced, and locomotor function improved after MSC infusion. These results suggest that intravenously delivered MSCs have important effects on reducing BSCB leakage which could contribute to their therapeutic efficacy.

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  • Profile analysis of mesenchymal stem cell for cellular therapy

    Grant number：25462226  2013.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Honmou Osamu, Wanibuchi Masahiko, Sasaki Masanori, Mikami Takeshi, Kobayashi Masaki, Nakazaki Masahito, Sakai Takuro, Sasaki Yuichi, Suzuki Junpei, Morita Tomonori, Namioka Ai, Namioka Takahiro

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    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    Recent progress in regenerative medicine for injured neural tissue have revealed that greater therapeutic efficacy can be achieved by stem cell therapy via multiple mechanisms for various disorders. Especially, it has been suggested that mesenchymal stem cells (MSCs) derived from bone marrow may represent a potential source for organ regeneration. In this study, cell biological analyses were performed with MSCs from human and rat bone marrow using several molecular, biochemical and genetics approaches. Therapeutic efficacy by rat MSCs in vivo was also examined with rat stroke model.

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  • Characteristic analysis of mesenchymal stem cells for regenerative medicine

    Grant number：24592138  2012.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    RIE Onodera, HONMOU Osamu, WANIBUCHI Masahiko, SASAKI Masanori, MIKAMI Takeshi, KOBAYASHI Masaki, NAKAZAKI Masahito, SAKAI Takurou, SASAKI Yuichi, SUZUKI Junpei, MORITA Tomonori

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    Grant amount：\5200000 （ Direct Cost: \4000000 、 Indirect Cost：\1200000 ）

    Recent advance in regenerative medicine have demonstrated that greater therapeutic efficacy can be obtained by stem cell therapy via multiple mechanisms compared to the standard therapies for various diseases. Especially, it has been suggested that bone marrow stem cells may represent an alternative source of neural progenitor cells for organ regeneration. Among bone marrow stem cells, much attention has been paid to mesenchymal stem cells (MSCs, also referred to as bone marrow stromal cells) because of their plasticity for differentiation into classical mesenchymal lineages, such as neuronal lineages. In this study, cell biological analyses were performed with MSCs from human and rat bone marrow using several molecular, biochemical and genetics approaches. Therapeutic efficacy with rat MSCs in vivo was also examined with rat stroke model.

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  • The Scientific Research Honor Society (Sigma Xi), full member

    2024.4

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    Type：Other

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