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Repairing mechanism of human mesenchymal stem cells (hMSCs) via immune regulation on ischemia brain injury

Research Project

Project/Area Number 25462236
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionShowa University

Principal Investigator

OHTAKI HIROKAZU  昭和大学, 医学部, 講師 (20349062)

Co-Investigator(Renkei-kenkyūsha) SHIODA SEIJI  星薬科大学, 先端生命科学研究所, 特任教授 (80102375)
Rakwal Randeep  筑波大学, 生命科学研究科, 教授 (70590850)
MIYAZAKI TAKURO  昭和大学, 医学部, 講師 (80398693)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords骨髄間葉系幹細胞 / 脳虚血 / マイクログリア / マイクロアレイ / 神経細胞死 / 移植細胞治療 / 炎症性サイトカイン
Outline of Final Research Achievements

Human bone marrow derived mesenchymal stem cells (hMSCs) attract the attention of tissue repair during several diseases. The purpose of the preset study is to determine the mechanism of hMSCs on tissue repair. In particular, we focused on the relationship between hMSCs and macrophages and microglia. hMSCs suppressed inducible nitric oxide synthase (iNOS) and NO production from BV-2 microglia after interferon-γ stimulation in the cell number dependent fashion. Moreover, by the transcriptome analysis, hMSCs cultured with ischemic hippocampal homogenate increased 98 transcriptomes including chemokines. Further analysis was determined a chemokine, CCL2 from hMSCs was regulated by inflammatory cytokines induced by ischemic stress.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (46 results)

All 2016 2015 2014 2013 Other

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (29 results) (of which Int'l Joint Research: 5 results) Book (4 results)

  • [Journal Article] Therapeutic effects and mechanism of conditioned media from human mesenchymal stem cells on anti-GBM glomerulonephritis in WKY rats.2016

    • Author(s)
      Iseri K, Iyoda M, Ohtaki H, Matsumoto K, Wada Y, Suzuki T, Yamamoto Y, Saito T, Hihara K, Tachibana S, Honda K, Shibata T.
    • Journal Title

      Am J Physiol Renal Physiol.

      Volume: 10 Issue: 11 Pages: 1152-1152

    • DOI

      10.1152/ajprenal.00165.2016

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) contributes to the proliferation of hematopoietic progenitor cells in murine bone marrow via PACAP-specific receptor.2016

    • Author(s)
      Xu Z, Ohtaki H, Watanabe J, Miyamoto K, Murai N, Sasaki S, Matsumoto M, Hashimoto H, Hiraizumi Y, Numazawa S, Shioda S.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 22373-22373

    • DOI

      10.1038/srep22373

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in adult mouse hippocampal neurogenesis after stroke.2016

    • Author(s)
      Matsumoto M, Nakamachi T, Watanabe J, Sugiyama K, Ohtaki H, Murai N, Sasaki S, Xu Z, Hashimoto H, Seki T, Miyazaki A, Shioda S.
    • Journal Title

      J Mol Neurosci

      Volume: 10 Issue: 2 Pages: 1007-1007

    • DOI

      10.1007/s12031-016-0731-x

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] PACAP38 suppresses cortical damage in mice with traumatic brain injury by enhancing antioxidant activity.2014

    • Author(s)
      Miyamoto K, Tsumuraya T, Ohtaki H, Dohi K, Satoh K, Xu Z, Tanaka S, Murai N, Watanabe J, Sugiyama K, Aruga T, Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment and Characterization of Primary Adult Microglial Culture in Mice2013

    • Author(s)
      Ohtaki H, Tsumuraya T, Song D, Sato A, Ohara K, Miyamoto K, Nakano H, Kiriyama K, Dohi K, Hiraizumi H, Matsunaga M, Shioda S
    • Journal Title

      Acta Neurochir Suppl

      Volume: 118 Pages: 49-54

    • DOI

      10.1007/978-3-7091-1434-6_8

    • ISBN
      9783709114339, 9783709114346
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Therapeutic effects of human mesenchymal stem cells in wistar-kyoto rats with anti-glomerular basement membrane glomerulonephritis.2013

    • Author(s)
      Suzuki T, Iyoda M, Shibata T, Ohtaki H, Matsumoto K, Shindo-Hirai Y, Kuno Y, Wada Y, Yamamoto Y, Kawaguchi M, Shioda S, Akizawa T.
    • Journal Title

      PLoS One

      Volume: 24 Issue: 6 Pages: e67475-e67475

    • DOI

      10.1371/journal.pone.0067475

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] PACAP Attenuates NMDA-Induced Retinal Damage in Association with Modulation of the Microglia/Macrophage Status into an Acquired Deactivation Subtype.2013

    • Author(s)
      Wada Y, Nakamachi T, Endo K, Seki T, Ohtaki H, Tsuchikawa D, Hori M, Tsuchida M, Yoshikawa A, Matkovits A, Kagami N, Imai N, Fujisaka S, Usui I, Tobe K, Koide R, Takahashi H, Shioda S
    • Journal Title

      J Mol Neurosci.

      Volume: 51(2) Issue: 2 Pages: 493-502

    • DOI

      10.1007/s12031-013-0017-5

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activation of microglia induces symptoms of Parkinson's disease in wild-type, but not in IL-1 knockout mice.2013

    • Author(s)
      Tanaka S, Ishii A, Ohtaki H, Shioda S, Yoshida T, Numazawa S.
    • Journal Title

      J Neuroinflammation.

      Volume: 10 Issue: 1 Pages: 143-143

    • DOI

      10.1186/1742-2094-10-143

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Low dose of methylmercury (MeHg) exposure induces caspase mediated-apoptosis in cultured neural progenitor cells.2013

    • Author(s)
      Watanabe J, Nakamachi T, Ohtaki H, Naganuma A, Shioda S, Nakajo S.
    • Journal Title

      J Toxicol Sci.

      Volume: 38 Pages: 931-935

    • NAID

      130004447097

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Status of Systemic Oxidative Stress during Therapeutic Hypothermia in Patients with Post-Cardiac Arrest Syndrome.2013

    • Author(s)
      Dohi K, Miyamoto K, Fukuda K, Nakamura S, Hayashi M, Ohtaki H, Shioda S, Aruga T
    • Journal Title

      Oxid Med Cell Longev.

      Volume: 2013 Pages: 562429-562429

    • DOI

      10.1155/2013/562429

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The anti-inflammatory property of human bone marrow-derived mesenchymal stem/stromal cells is preserved in late-passage cultures.2013

    • Author(s)
      Song D, Ohtaki H, Tsumuraya T, Miyamoto K, Shibato J, Rakwal R, Xu Z, Hiraizumi Y, Inoue T, Shioda S
    • Journal Title

      J Neuroimmunol.

      Volume: 263(1-2) Issue: 1-2 Pages: 55-63

    • DOI

      10.1016/j.jneuroim.2013.07.018

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Edaravone Increases Regional Cerebral Blood Flow After Traumatic Brain Injury in Mice2013

    • Author(s)
      Miyamoto K, Ohtaki H, Dohi K, Tsumuraya T, Nakano H, Kiriyama K, Song D, Aruga T, Shioda S
    • Journal Title

      Acta Neurochir Suppl

      Volume: 118 Pages: 103-9

    • DOI

      10.1007/978-3-7091-1434-6_18

    • ISBN
      9783709114339, 9783709114346
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Therapeutic time window for edaravone treatment of traumatic brain injury in mice.2013

    • Author(s)
      Miyamoto K, Ohtaki H, Dohi K, Tsumuraya T, Song D, Kiriyama K, Satoh K, Shimizu A, Aruga T, Shioda S
    • Journal Title

      Biomed Res Int.

      Volume: 2013 Pages: 379206-379206

    • DOI

      10.1155/2013/379206

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] エクリン汗腺におけるPACAPの汗分泌促進作用2016

    • Author(s)
      渡邊 潤, 佐々木 駿, 中町 智哉, 大滝 博和, 荒田 悟, 本田 一穂, 塩田 清二
    • Organizer
      第13回GPCR研究会
    • Place of Presentation
      未来科学館,東京
    • Year and Date
      2016-05-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] 脳虚血ホモジネート刺激によるヒト骨髄間葉系幹・前駆細胞(hMSCs)のCCL2産生機構の解明2016

    • Author(s)
      大滝博和、渡邊潤、谷口紗季、本田一穂
    • Organizer
      第121回日本解剖学会総会・全国学術集会
    • Place of Presentation
      ビックパレットふくしま,郡山
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] エクリン汗腺におけるPACAPの汗分泌促進作用2016

    • Author(s)
      渡邊 潤, 佐々木 駿, 中町 智哉, 大滝 博和, 荒田 悟, 本田 一穂, 塩田 清二
    • Organizer
      第121回日本解剖学会総会・全国学術集会
    • Place of Presentation
      ビックパレットふくしま,郡山
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] Crucial role of PACAP in neural progenitor cells during development and after degeneration.2015

    • Author(s)
      Watanabe J, Ohtaki H, Nakamachi T, Matsumoto M, Sasaki S, Murai M, Arata S, Shioda S.
    • Organizer
      Neuropeptides 2015
    • Place of Presentation
      Aberdeen, UK
    • Year and Date
      2015-09-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of PACAP on the secretions of tear and saliva in mouse.2015

    • Author(s)
      Nakamachi T, Watanabe J, Seki T, Ohtaki H, Shioda S
    • Organizer
      Neuropeptides 2015
    • Place of Presentation
      Aberdeen, UK
    • Year and Date
      2015-09-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PACAP contributes to proliferation of hematopoietic stem/progenitor cells in murine bone marrow.2015

    • Author(s)
      Ohtaki H, Xu Z, Watanabe J, Hiraizumi Y, Hashimoto H, Numazawa S, Shioda S.
    • Organizer
      12th international symposium on VIP/PACAP and related peptides
    • Place of Presentation
      Cappadocia, Turkey
    • Year and Date
      2015-09-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ACAP contributes proliferation of hippocampal neural stem/progenitor cells after global ischemi in mice2015

    • Author(s)
      Nakamachi T, Ohtaki H, Watanabe J, Shioda S.
    • Organizer
      12th international symposium on VIP/PACAP and related peptides
    • Place of Presentation
      Cappadocia, Turkey
    • Year and Date
      2015-09-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Involvement of PACAP in differentiation of neural progenitor cells via radial glia2015

    • Author(s)
      Watanabe J, Ohtaki H, Nakamachi T, Sasaki S, Matsumoto M, Murai N, Seki T, Arata S, Shioda S.
    • Organizer
      12th international symposium on VIP/PACAP and related peptides
    • Place of Presentation
      Cappadocia, Turkey
    • Year and Date
      2015-09-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression and localization of PACAP specific receptor (PAC1R) in the mouse bone marrow.2015

    • Author(s)
      徐枝芳,大滝博和,渡邊潤,平泉裕,沼澤聡,塩田清二
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム,東京
    • Year and Date
      2015-07-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト骨髄間葉系幹細胞はPACAPを介して脊髄損傷後の炎症を調節する。2015

    • Author(s)
      大滝博和, 圓谷智海, 徐枝芳, 渡邊潤, 佐藤敦, 平泉裕, 橋本均, 塩田清二
    • Organizer
      第80回日本インターフェロン・サイトカイン学会大会
    • Place of Presentation
      東京工業大学,東京
    • Year and Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 糖尿病モデルマウスに対する骨髄由来ヒト間葉系幹細胞(hMSCs)の膵臓内投与における有用性の検討2015

    • Author(s)
      村井謙允,大滝博和,渡邊潤,佐々木駿,松本皆子,泉崎雅彦
    • Organizer
      第320回昭和大学学士会例会
    • Place of Presentation
      昭和大学,東京
    • Year and Date
      2015-05-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腺におけるPituitary Adenylate Cyclase Activating Polypeptide (PACAP)の汗分泌促進効果2015

    • Author(s)
      佐々木駿,渡邊潤,大滝博和,松本皆子,村井謙允,宮崎章
    • Organizer
      第320回昭和大学学士会例会
    • Place of Presentation
      昭和大学,東京
    • Year and Date
      2015-05-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Pituitary adenylate cyclase activating polypeptide (PACAP)の成体海馬神経新生・再生への関与について2015

    • Author(s)
      松本皆子,渡邊潤,村井謙允,佐々木,大滝博和,宮崎章
    • Organizer
      第320回昭和大学学士会例会
    • Place of Presentation
      昭和大学,東京
    • Year and Date
      2015-05-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] PACAP contributes to the proliferation of hematopoietic stem/progenitor cells in murine bone marrow via its specific receptor PAC1.2015

    • Author(s)
      Xu Z, Ohtaki H, Watanabe J, Nakamachi T, Numazawa S, Shioda S.
    • Organizer
      第12回GPCR研究会
    • Place of Presentation
      未来科学館,東京
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 神経前駆細胞に対するグレリンの作用の解析2015

    • Author(s)
      渡邊潤, 影山晴秋, 大滝博和, 松本皆子, 佐々木駿, 村井謙允, 荒田悟, 塩田清二
    • Organizer
      第12回GPCR研究会
    • Place of Presentation
      未来科学館,東京
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] PACAPの抗酸化誘導作用と加齢性神経変性との関連2014

    • Author(s)
      中町智哉,大滝博和,渡邊潤,吉川輝,土田将史,杉山公一,加賀美信幸,今井ノリ,塩田清二
    • Organizer
      第119回日本解剖学会総会・全国学術集会
    • Place of Presentation
      栃木・下野
    • Related Report
      2013 Research-status Report
  • [Presentation] Expression of PACAP/VIP and their receptors in the mouse bone marrow2014

    • Author(s)
      徐枝芳,大滝博和,中町智哉,渡邊潤,宋丹丹,宮本和幸,平泉裕,沼澤聡,塩田清二
    • Organizer
      第119回日本解剖学会総会・全国学術集会
    • Place of Presentation
      栃木・下野
    • Related Report
      2013 Research-status Report
  • [Presentation] 脳虚血刺激によるヒト骨髄間葉系幹細胞の応答2014

    • Author(s)
      大滝博和,谷口紗季,徐枝芳,渡邊潤,宋丹丹,宮本和幸,塩田 清二
    • Organizer
      第119回日本解剖学会総会・全国学術集会
    • Place of Presentation
      栃木・下野
    • Related Report
      2013 Research-status Report
  • [Presentation] 頭部外傷モデルマウスにおけるMRIを用いた神経障害の解析2014

    • Author(s)
      渡邊潤,大滝博和,Darwin J Prockop, 塩田清二
    • Organizer
      第119回日本解剖学会総会・全国学術集会
    • Place of Presentation
      栃木・下野
    • Related Report
      2013 Research-status Report
  • [Presentation] マウス頭部外傷におけるPACAPの神経保護作用についての検討2014

    • Author(s)
      宮本和幸,大滝博和,土肥謙二,佐藤和恵,宋丹丹,徐枝芳,村井謙充,渡邉潤,田中佐知子,有賀徹,塩田清二
    • Organizer
      第119回日本解剖学会総会・全国学術集会
    • Place of Presentation
      栃木・下野
    • Related Report
      2013 Research-status Report
  • [Presentation] Expression and localization of PACAP specific receptor PAC1R in mouse bone marrow2014

    • Author(s)
      徐 枝芳、大滝 博和、渡邊 潤、宮本 和幸、村井謙允、中町 智哉、平泉 裕、沼澤 聡、塩田 清二
    • Organizer
      第11回GPCR研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Expression and localization of PACAP specific receptor (PAC1R) in bone marrow of mice2014

    • Author(s)
      徐 枝芳、大滝 博和、渡邊 潤、宮本 和幸、村井謙允、中町 智哉、平泉 裕、沼澤 聡、塩田 清二
    • Organizer
      第35回日本炎症・再生医学会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report
  • [Presentation] 脊髄損傷マウスにおけるマイクログリア/マクロファージ活性化へのインターロイキン1の関与2013

    • Author(s)
      佐藤敦,大滝博和,小原賢司,圓谷智海,平泉裕,渥美敬,塩田清二
    • Organizer
      第86回日本整形外科学会学術総会
    • Place of Presentation
      広島,広島
    • Related Report
      2013 Research-status Report
  • [Presentation] Effect of water intake on heatstroke of mice.2013

    • Author(s)
      Miyamoto K, Ohtaki H, Miyake Y, Shioda S, Aruga T
    • Organizer
      7th Asian Conference on Emergency Medicine (ACEM)
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] Human bone marrow-derived mesenchymal stem cells suppressed classical activation of microglial cells2013

    • Author(s)
      Ohtaki H, Song D, Xu Z, Miyamoto K, Shibato J, Rakwal R, Dohi K, Hiraizumi Y, Shioda S
    • Organizer
      Neuroscience meeting SFN2013
    • Place of Presentation
      San Diego, CA
    • Related Report
      2013 Research-status Report
  • [Presentation] Human stem/progenitor cells from bone marrow improve spinal cord injury via communicating with PACAP.2013

    • Author(s)
      Ohtaki H, Tsumuraya T, Song D, Sato A, Xu Z, Miyamoto K, Hiraizumi Y, Nakamachi T, Hashimoto H, Shintani N, Shioda S
    • Organizer
      The 11th International Symposium on VIP, PACAP and Related Peptides
    • Place of Presentation
      Pecs, Hungary
    • Related Report
      2013 Research-status Report
  • [Presentation] PACAP stimulates the corneal healing via lacrimal-mediating and direct pathways in mouse.2013

    • Author(s)
      Nakamachi T, Seki T, Wada Y, Ohtaki H, Kagami N, Imai N, Arata S, Hashimoto H, Shintani N, Farkas J, Matkovits A, Reglodi D, Shioda S
    • Organizer
      The 11th International Symposium on VIP, PACAP and Related Peptides
    • Place of Presentation
      Pecs, Hungary
    • Related Report
      2013 Research-status Report
  • [Presentation] The anti-inflammatory property of human bone marrow-derived mesenchymal stem cells is preserved in late-passage cultures.

    • Author(s)
      Ohtaki H, Song D, Tsumuraya T, Miyamoto K, Shibato J, Rakwal R, Xu Z, Inoue T, Shioda S
    • Organizer
      6th International Symposium on mesenchymal stem/progenitor cells
    • Place of Presentation
      College Station, TX
    • Related Report
      2013 Research-status Report
  • [Presentation] Localization of pituitary adenylate cyclase-activating polypeptide (PACAP) receptor (PAC1R) in bone marrow of mice

    • Author(s)
      徐枝芳,大滝博和,中町智哉,渡邊潤,塩田清二
    • Organizer
      日本解剖学会関東支部第101回学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Book] Pituitary Adenylate Cyclase Activating Polypeptide - PACAP, (Eds. Reglodi D and Tamas A)2016

    • Author(s)
      Ohtaki H and Shioda S.
    • Publisher
      Springer Nature (New York)
    • Related Report
      2015 Annual Research Report
  • [Book] Handbook of Hormones: Comparative and General Endocrinology (Eds. Takei Y, Ando H, Tsutsui K)2016

    • Author(s)
      Ohtaki H
    • Total Pages
      6
    • Publisher
      Elsevier (USA)
    • Related Report
      2015 Annual Research Report
  • [Book] 最新臨床脳卒中学(上)7月号増刊2014

    • Author(s)
      大滝博和,渡邊潤,塩田清二
    • Total Pages
      3
    • Publisher
      日本臨床社
    • Related Report
      2013 Research-status Report
  • [Book] Neuroanesthesia and Cerebro-Spinal Protection (Hiroyuki Uchino, Kazuo Ushijima, Yukiko Ikeda eds)2014

    • Author(s)
      Ohtaki H, Shioda S
    • Total Pages
      8
    • Publisher
      Springer (Tokyo)
    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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