• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2007 Fiscal Year Final Research Report Summary

Neural induction of somatic stem cells / ES cells by VHL gene /peptide and application to regenerative medicine

Research Project

Project/Area Number 16390415
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

KANNO Hiroshi  Yokohama City University, Graduate School of Medicine, Associate Professor (40244496)

Co-Investigator(Kenkyū-buntansha) NAGASHIMA Yoji  Yokohama City University, Graduate School of Medicine, Associate Professor (10217995)
YAMAMOTO Isao  Yokohama City Univeisity, Graduate School of Medicine, Professor (30158266)
DEZAWA Mari  Kyoto University, Associate Professor (50272323)
SUGIMOTO Naoki  Konan University, School of Physical Science and Engineering, Professor (60206430)
NAKANO Shuichi  Konan University, Frontier Institute for Biological Engineering, Assistant Professor (70340908)
Project Period (FY) 2004 – 2007
Keywordssomatic stem cell / VHL protein / protein transduction domain / neural induction / BC-box motif / regenerative therapy / neuronal disease / peptide
Research Abstract

Several somatic stem cells have potential to differentiate to neurons, and they are hopeful to be used as grafted donor cells for neuronal regenerative therapy. However, the grated cells little survive and differentiate to functional neurons in recipient neural tissue. To overcome the problem, neural induction using neurotrophic factors or gene transfer has been employed before grafting, but neurotrophic factors do not occur specific neural induction, while gene transfer has risk of vector. If a neural induction domain for somatic stem cells exists in proteins to induce neural differentiation, its identification can contribute to neuronal regenerative therapy through neural induction of somatic stem cells using the neural induction domain. We previously demonstrated that von Hippel-Lindau tumor suppressor(VHL)protein has a function of neural induction in neural stem cells(NSCs)without any neurotrophic factors. Then, we hypothesized that a neural induction domain potentially exists in t … More he VHL protein. Here we identify a neural induction domain for somatic stem cells in the VHL protein, and show neural induction of the cells by transfer of the domain peptide linked to protein transduction domain(PTD). The neural induction domain in the VHL protein contains BC-box motif[(A,P,S,T)XX(A,C)XXX(A,I,L,V)]corresponding to binding site of elongin BC, which is evolutionary conserved from virus to mammalian.Therefore, we proposed that other BC-box proteins also contain the neural induction domain, and subsequently show to identify the neural induction domains at amino-acid sequences encoded by BC-box motif within BC-box proteins responsible for neural induction of somatic stem cells. In addition, we show that the domain has the same function for other somatic stem cells except for neural stem cells. Furthermore, when the domain peptide-transferred stem cells are grafted into recipient nervous tissue in neuronal disease models, the grafted cells differentiate to neurons and neuronal repair for neuronal disease models is achieved. Thus, a neural induction domain is identified at BC-box motif in BC-box proteins. The neural induction of somatic stem cells is caused by intracellular delivery of the neural induction domain peptide linked to PTD, and would contribute to neuronal regenerative therapy. Less

  • Research Products

    (27 results)

All 2007 2006 2005 2004

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (13 results) Book (1 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Journal Article] Ca2+-activated K+ channels in human melanoma cells are up-regulated by hypoxia involving hypoxia-inducible factor-lalpha and the von Hippel-Lindau protein2006

    • Author(s)
      Tajima N, Schonherr K, Niedling S, Kaatz M, Kanno H, Schonherr R, Heinemann SH
    • Journal Title

      J Physiol 571(Pt 2)

      Pages: 349-359

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Ca2+-activated K+ channels in human melanoma cells are up-regulated by hypoxia involving hypoxia-inducible factor-lalpha and the von Hippel-Lindau protein2006

    • Author(s)
      Tajima, N., Schonherr, K., Niedling, S., Kaatz, M., Kanno, H., Schonherr, R., Heinemann, S.H
    • Journal Title

      571(Pt2)

      Pages: 349-359

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Behavioral and histological evaluation of a focalcerebral infarction rat model transplanted with neurons induced from bone marrow stromal cells2005

    • Author(s)
      Mimura T, Dezawa M, Kanno H, Yamamoto I.
    • Journal Title

      J Neuropathol Exp Neurol 64(12)

      Pages: 1108-1117

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] The role of von Hippel-Lindau protein in the differentiation of neural progenitor cells under normoxic and anoxic conditions2005

    • Author(s)
      Tanaka Y, Kanno H, Dezawa M, Mimura T, Kubo A, Yamamoto I
    • Journal Title

      Neurosci Lett 383(1-2)

      Pages: 28-32

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Behavioral and histological evaluation of a focal cerebral infarction rat model transplanted with neurons induced from bone marrow stromal cells2005

    • Author(s)
      Mimura, T., Dezawa, M., Kanno, H., Yamamoto, I
    • Journal Title

      J Neuropathol Exp Neurol 64(12)

      Pages: 1108-1117

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The role of von Hippel-Lindau protein in the differentiation of neural progenitor cells under normoxic and anoxic conditions2005

    • Author(s)
      Tanaka, Y., Kanno, H., Dezawa, M., Mimura, T., Kubo, A., Yamamoto, I
    • Journal Title

      Neurosci Lett 383(1-2)

      Pages: 28-32

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation2004

    • Author(s)
      Dezawa M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, Tajima N, Yamada H, Sawada H, Ishikawa H, Mimura T, Kitada M, Suzuki Y, Ide C
    • Journal Title

      J Clin Invest 113(12)

      Pages: 1701-1710

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Peripheral nerve regeneration by transplantation of bone mar row stromal cell-derived Schwann cells in adult rats2004

    • Author(s)
      Mimura T, Dezawa M, Kanno H, Sawada H, Yamamoto I
    • Journal Title

      J Neurosurg 101(5)

      Pages: 806-812

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transp lantation2004

    • Author(s)
      Dezawa, M., Kanno, H., Hoshino, M.,Cho, H., Matsumoto, N., Itokazu, Y., Tajima, N., Yamada, H., Sawada, H., Ishikawa, H., Mimura, T., Kitada, M., Suzuki, Y., Ide, C
    • Journal Title

      J Clin Invest 113(12)

      Pages: 1701-1710

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Peripheral nerve regeneration by transplantation of bone marrow stromal cell-derived Schwann cells in adult rats2004

    • Author(s)
      Mimura, T., Dezawa, M., Kanno, H., Sawada, H., Yamamoto, I
    • Journal Title

      J Neurosurg 101(5)

      Pages: 806-812

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Neural induction of bone marrow stem cells using gene/protein transfer and application for neural regeneration.2007

    • Author(s)
      Kanno, H
    • Organizer
      The 2nd International Conference on Stem Cells
    • Place of Presentation
      Agrigento, Italy
    • Year and Date
      20071000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Transplantation of VHL peptide-transferred neural stem cells promote recovery in injured rat spinal cord2007

    • Author(s)
      Maeda K, Kanno H, Yamazaki Y, Kubo A, Saito T
    • Organizer
      The 53rd Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      米国、サンディエゴ市
    • Year and Date
      20070200
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Transplanted VHL peptide-transferred bone marrow stromal cells promote recovery in injured rat spinal cord2007

    • Author(s)
      Yamazaki Y, Maeda K, Kanno H, Saito T
    • Organizer
      The 53rd Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      米国、サンディエゴ市
    • Year and Date
      20070200
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Transplantation of VHL peptide-transferred neural stem cells promote recovery in injured rat spinal cord2007

    • Author(s)
      Maeda, K., Kanno, H., Yamazaki, Y., Kubo, A., Saito, T
    • Organizer
      The 53rd Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      San Diego, USA
    • Year and Date
      20070200
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Transplanted VHL peptide-transferred bone marrow stromal cells promote recovery in injured rat spinal cord2007

    • Author(s)
      Yamazaki, Y., Maeda, K., Kanno, H., Saito, T
    • Organizer
      The 53rd Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      San Diego, USA
    • Year and Date
      20070200
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Neural induction of bone marrow stem cells using gene/protein transfer and application for neural regeneration2007

    • Author(s)
      Kanno H
    • Organizer
      The 2th International Conference on Stem Cells
    • Place of Presentation
      イタリア共和国、アグリジェント市
    • Year and Date
      2007-10-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 神経分化を誘導する機能的ペプチドを用いた神経再生療法の開発2006

    • Author(s)
      菅野 洋、久保 篤彦、味村 俊郎、山本 勇夫、前田 和彦、山崎 吉以、蓮見 由紀子、有江 裕子、松本 大輔、小林 菜穂子、吉田 徹彦
    • Organizer
      第44回日本人工臓器学会
    • Place of Presentation
      横浜市
    • Year and Date
      20061100
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] VHL蛋白導入による組織細胞の神経分化誘導とその再生医学への応用2006

    • Author(s)
      菅野 洋、久保 篤彦、味村 俊郎、山本 勇夫、前田 和彦、山崎 吉以、蓮見 由紀子、有江 裕子、松本 大輔、小林 菜穂子、吉田 徹彦
    • Organizer
      第65回日本脳神経外科学会総会
    • Place of Presentation
      京都市
    • Year and Date
      20061000
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Role of VHL protein in neuron differentiation of multipotent stem cells and its application for neuronal regeneration2006

    • Author(s)
      Kanno H
    • Organizer
      7th international VHL symposium
    • Place of Presentation
      カナダ、ロンドン市
    • Year and Date
      20061000
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Role of VHL protein in neuronal differentiation of multipotent stem cells and its application for neuronal regeneration2006

    • Author(s)
      Kanno, H
    • Organizer
      7th international VHL symposium
    • Place of Presentation
      London, Canada
    • Year and Date
      20061000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] VHL遺伝子/ペプチド導入繊幹細胞を用いた神経再生療法2006

    • Author(s)
      菅野 洋、久保 篤彦、味村 俊郎、横山 高玲、山本 勇夫、前田 和彦、山崎 吉以、齋藤 知行、川中 紀邦、水木 信久、長瀬 敬、松本 大輔、小林 菜穂子、吉田 徹彦
    • Organizer
      第5回日本再生医療学会
    • Place of Presentation
      岡山市
    • Year and Date
      20060300
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 体性幹細胞を用いた神経再生医療2005

    • Author(s)
      菅野 洋
    • Organizer
      第47回神奈川医学会学術大会
    • Place of Presentation
      横浜市
    • Year and Date
      20051100
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] VHL遺伝子/ペプチド導入体性幹細胞を用いた神経再生療法の開発2005

    • Author(s)
      菅野 洋、久保 篤彦、味村 俊郎、横山 高玲、山本 勇夫、前田 和彦、山崎 吉以、長瀬 敬、松本 大輔、小林 菜穂子、吉田 徹彦
    • Organizer
      第64回日本脳神経外科学会
    • Place of Presentation
      横浜市
    • Year and Date
      20051000
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 先端医療シリーズ29「脳神経外科の最新医療」2004

    • Author(s)
      菅野 洋, ほか
    • Total Pages
      390
    • Publisher
      先端医療技術研究所
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] VHL peptide2007

    • Inventor(s)
      Kanno H
    • Industrial Property Rights Holder
      Kanno Toagosei co, Ltd.
    • Industrial Property Number
      US 7214767
    • Acquisition Date
      2007-05-08
    • Description
      「研究成果報告書概要(和文)」より
    • Overseas
  • [Patent(Industrial Property Rights)] 神経分化誘導ペプチド及びその利用2005

    • Inventor(s)
      菅野 洋, 吉田 徹彦, 小林 菜穂子
    • Industrial Property Rights Holder
      菅野 洋、東亜合成株式会社
    • Industrial Property Number
      特願2005-276795
    • Filing Date
      2005-08-11
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] VHL peptide2005

    • Inventor(s)
      Kanno H
    • Industrial Property Rights Holder
      Kanno Toagosei co, Ltd.
    • Industrial Property Number
      US 7214767
    • Filing Date
      2005-05-25
    • Description
      「研究成果報告書概要(和文)」より
    • Overseas

URL: 

Published: 2010-02-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi