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2013 Fiscal Year Final Research Report

Autologous Bone Marrow Stromal Cell Transplantation for Stroke: Steps to Standardize the Clinical Protocols

Research Project

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Project/Area Number 23390342
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionHokkaido University

Principal Investigator

SHICHINOHE Hideo  北海道大学, 大学病院, 助教 (80374479)

Co-Investigator(Kenkyū-buntansha) HOUKIN Kiyohiro  北海道大学, 北海道大学病院, 教授 (90229146)
KURODA Satoshi  富山大学, 大学院・医学薬学研究部(医学), 教授 (10301904)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords移植・再生医療 / 脳神経外科 / 骨髄間質細胞 / 脳梗塞
Research Abstract

Human bone marrow stromal cells (BMSCs) were cultured with human platelet lysate (hPL) instead of fetal calf serum (FCS). Their production of growth factors was quantified with ELISA. The BMSCs were labeled with superparamagnetic iron oxide (SPIO). Rat permanent focal ischemia models were made and BMSCs were injected into the ipsilateral striatum 7 days post-insult. There was no difference in cell proliferation between the BMSCs cultured with hPL and FCS. The BMSC-hPL produced not less amount of BDNF, HGF, NGF, PDGF-BB and TGF-beta1. Rotarod test showed that the motor function deteriorated after ischemia and BMSC transplantation enhanced the recovery. MRI demonstrated that the SPIO-BMSCs migrated towards the lesion. 18F-FDG PET showed that the recovery of glucose utilization was promoted. The hPL may be valuable and safe in expanding BMSCs. The application of bio-imaging techniques are also valuable for BMSC transplantation against stroke.

  • Research Products

    (22 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (8 results) (of which Invited: 4 results) Remarks (1 results)

  • [Journal Article] Bone Marrow Stromal Cells Rescue Ischemic Brain by Trophic Effects and Phenotypic Change Toward Neural Cells2014

    • Author(s)
      Shichinohe H, Ishihara T, Takahashi K, Tanaka Y, Miyamoto M, Yamauchi T, Saito H, Takemoto H, Houkin K, Kuroda S
    • Journal Title

      Neurorehabil Neural Repair

    • Peer Reviewed
  • [Journal Article] Bone marrow stromal cell transplantation enhances recovery of motor function after lacunar stroke in rats2013

    • Author(s)
      Shichinohe H, Yamauchi T, Saito H, Houkin K, Kuroda S
    • Journal Title

      Acta Neurobiol Exp

      Volume: 73 Pages: 354-363

    • Peer Reviewed
  • [Journal Article] I-Iomazenil Single Photon Emission Computed Tomography Visualizes Recovery of Neuronal Integrity by Bone Marrow Stromal Cell Therapy in Rat Infarct Brain2013

    • Author(s)
      Saito H, Magota K, Zhao S, Kubo N, Kuge Y, Shichinohe H, Houkin K, Tamaki N, Kuroda S
    • Journal Title

      Stroke

      Volume: 44 Pages: 2869-2874

    • Peer Reviewed
  • [Journal Article] Bone marrow stromal cell transplantation enhances recovery of local glucose metabolism after cerebral infarction in rats : a serial 18F-FDG PET study2013

    • Author(s)
      Miyamoto M, Kuroda S, Zhao S, Magota K, Shichinohe H, Houkin K, Kuge Y, Tamaki N
    • Journal Title

      J Nucl Med

      Volume: 54 Pages: 145-150

    • Peer Reviewed
  • [Journal Article] Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct2013

    • Author(s)
      Kawabori M, Kuroda S, Ito M, Shichinohe H, Houkin K, Kuge Y, Tamaki N
    • Journal Title

      Neuropathology

      Volume: 33 Pages: 140-148

    • Peer Reviewed
  • [Journal Article] Visualization of the superparamagnetic iron oxide (SPIO) -labeled bone marrow stromal cells using a 3.0-T MRI-a pilot study for clinical testing of neurotransplantation2012

    • Author(s)
      Shichinohe H, Kuroda S, Kudo K, Ito M, Kawabori M, Miyamoto M, Nakanishi M, Terae S, Houkin K
    • Journal Title

      Transl. Stroke Res

      Volume: 3 Pages: 99-106

    • Peer Reviewed
  • [Journal Article] Intracerebral, but not intravenous, transplantation of bone marrow stromal cells enhances functional recovery in rat cerebral infarct : an optical imaging study2012

    • Author(s)
      Kawabori M, Kuroda S, Sugiyama T, Ito M, Shichinohe H, Houkin K, Kuge Y, Tamaki N
    • Journal Title

      Neuropathology

      Volume: 32 Pages: 217-26

    • Peer Reviewed
  • [Journal Article] Impact of ageing on biological features of bone marrow stromal cells (BMSC) in cell transplantation therapy for CNS disorders : functional enhancement by granulocyte-colony stimulating factor (G-CSF)2012

    • Author(s)
      Chiba Y, Kuroda S, Osanai T, Shichinohe H, Houkin K, Iwasaki Y
    • Journal Title

      Neuropathol

      Volume: 32 Pages: 139-148

    • Peer Reviewed
  • [Journal Article] Therapeutic effects of intra-arterial delivery of bone marrow stromal cells in traumatic brain injury of rats--in vivo cell tracking study by near-infrared fluorescence imaging2012

    • Author(s)
      Osanai T, Kuroda S, Sugiyama T, Kawabori M, Ito M, Shichinohe H, Kuge Y, Houkin K, Tamaki N, Iwasaki Y
    • Journal Title

      Neurosurg

      Volume: 70 Pages: 435-444

    • Peer Reviewed
  • [Journal Article] Biological features of human bone marrow stromal cells (hBMSC) cultured with animal protein-free medium -safety and efficacy of clinical use for neurotransplantation2011

    • Author(s)
      Shichinohe H, Kuroda S, Sugiyama T, Ito M, Kawabori M, Nishio M, Takeda Y, Koike T, Houkin K
    • Journal Title

      Transl. Stroke Res

      Volume: 2 Pages: 307-315

    • Peer Reviewed
  • [Journal Article] Validity of bone marrow stromal cell expansion by animal serum-free medium for cell transplantation therapy of cerebral infarct in rats-A serial MRI study2011

    • Author(s)
      Ito M, Kuroda S, Sugiyama T, Shichinohe H, Takeda Y, Nishio M, Koike T, Houkin K
    • Journal Title

      Transl. Stroke Res

      Volume: 2 Pages: 294-306

    • Peer Reviewed
  • [Journal Article] Therapeutic impact of human bone marrow stromal cells expanded by animal serum-free medium for cerebral infarct in rats2011

    • Author(s)
      Sugiyama T, Kuroda S, Takeda Y, Nishio M, Ito M, Shichinohe H, Koike T
    • Journal Title

      Neurosurg

      Volume: 68 Pages: 1733-1742

    • Peer Reviewed
  • [Journal Article] Near-infrared fluorescence labeling allows noninvasive tracking of bone marrow stromal cells transplanted into rat infarct brain2011

    • Author(s)
      Sugiyama T, Kuroda S, Osanai T, Shichinohe H, Kuge Y, Ito M, Kawabori M, Iwasaki Y
    • Journal Title

      Neurosurg

      Volume: 68 Pages: 1036-1047

    • Peer Reviewed
  • [Presentation] Neuroprotective Effects of Cilostazol through the Multi-mechanisms in Mice Permanent Focal Ischemia2014

    • Author(s)
      Shichinohe H, et al
    • Organizer
      International Stroke Conference 2014
    • Place of Presentation
      San Diego Convention Center (San Diego, USA)
    • Year and Date
      20140212-14
  • [Presentation] Bone marrow stromal cell transplantation ameliorates motor deficit in rat lacunar infarct model2013

    • Author(s)
      Shichinohe H, et al
    • Organizer
      Neuroscience
    • Place of Presentation
      San Diego Convention Center (San Diego, USA)
    • Year and Date
      20131109-13
  • [Presentation] Bone marrow stromal cells serve "nursing effect" to damaged neurons by secreting neurotrophic factors in vitro and in vivo2013

    • Author(s)
      Shichinohe H, et al
    • Organizer
      International Stroke Conference 2013
    • Place of Presentation
      Hawaii Convention Center(Honolulu, USA)
    • Year and Date
      20130206-08
  • [Presentation] 自家骨髄間質細胞移植による脳梗塞再生医療をめざして2013

    • Author(s)
      七戸秀夫, 寳金清博
    • Organizer
      第31回日本神経治療学会総会シンポジウム3「進化する脳卒中治療1 -新たなステージへ-」
    • Place of Presentation
      東京ドームホテル(東京)
    • Year and Date
      2013-11-22
    • Invited
  • [Presentation] Platelet lysateで培養した骨髄間質細胞移植による脳梗塞再生医療2013

    • Author(s)
      七戸秀夫, 寳金清博
    • Organizer
      第37回日本血液事業学会総会シンポジウム3「再生医療の進歩」
    • Place of Presentation
      札幌コンベンションセンター (札幌市)
    • Year and Date
      2013-10-21
    • Invited
  • [Presentation] バイオイメージングを駆使した脳梗塞に対する再生医療2013

    • Author(s)
      七戸秀夫, 寳金清博, 黒田 敏
    • Organizer
      第41回日本磁気共鳴医学会大会シンポジウム3「分子イメージングにおけるBreakthrough 」
    • Place of Presentation
      アスティとくしま(徳島市)
    • Year and Date
      2013-09-20
    • Invited
  • [Presentation] 自家骨髄間質細胞移植による脳梗塞再生医療をめざして2013

    • Author(s)
      七戸秀夫, 黒田 敏, 寳金清博
    • Organizer
      第16回日本脳低温療法学会リフレッシングシンポジウム4(イブニングセミナー)「再生医療」
    • Place of Presentation
      キャッスルプラザ(名古屋市)
    • Year and Date
      2013-07-20
    • Invited
  • [Presentation] Steps to the Clinical Testing of Cell Transplantation for Stroke - Bone Marrow Stromal Cell Culture with Animal Protein-free Medium and Bio-imaging Using Clinical 3.0-Tesla MRI2012

    • Author(s)
      Shichinohe H, et al
    • Organizer
      International Stroke Conference 2012
    • Place of Presentation
      Ernest N. Morial Convention Center (New Orleans, USA)
    • Year and Date
      20120201-03
  • [Remarks]

    • URL

      http://www.neurosurgery-hokudai.jp/BMSC.html

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Published: 2015-06-25  

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