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Establishment of human hematopoietic system model mouse for understanding the regulatory mechanisms of human hematopoiesis.

Research Project

Project/Area Number 18500332
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionTokai University

Principal Investigator

YAHATA Takashi (2007)  Tokai University, School of Medicine, Assistant Professor (10398753)

中山 ゆかり (六車 ゆかり) (2006)  東海大学, 医学部, 特定研究員 (80398750)

Co-Investigator(Kenkyū-buntansha) ANDO Kiyoshi  Tokai University, School of Medicine, Professor (70176014)
八幡 崇  東海大学, 医学部, 助手 (10398753)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordshematopoietic stern cells / niche / humanized mouse / mesehcnymal stem cells / intra-bone marrow transplantation / cord blood / cell cycle / ヒトビモデンレマウス / 造血環境 / 造血制御
Research Abstract

Hematopoiesis is maintained by specificinteractions between both hematopoietic and non-hematopoietic cells. While hematopoietic stem cells (HSCs) have been extensively studied both in vitro and in vivo, little is known about the in vivo characteristics of stem cells of the non-hematopoietic component, known as mesenchymal stem cells (MSCs). Here we have visualized and characterized human MSCs in vivo following intramedullary transplantation of enhanced green fluorescent protein-marked human MSCs (eGFP-MSCs) into the bone marrow (BM) of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. During 4 to 10 weeks after transplantation, eGFP-MSCs that engrafted in murine BM integrated into the hematopoietic microenvironment (HME) of the host mouse. They differentiated into pericytes, myofibroblasts, BM stromal cells, osteocytes in bone, bone-lining osteoblasts, and endothelial cells, which constituted the functional components of the BM HME. The presence of human MSCs in murine BM resulted in increase in functionally and phenotypically primitive human hematopoietic cells. Human MSC-derived cells that reconstituted the hematopoietic microenvironment appeared to contribute to the maintenance of human hematopoiesis by actively interacting with primitive human hematopoietic cells.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (28 results)

All 2008 2007 2006

All Journal Article (19 results) (of which Peer Reviewed: 9 results) Presentation (9 results)

  • [Journal Article] Humanizing bone marrow in immune-deficient mice2008

    • Author(s)
      Ando K, et. al.
    • Journal Title

      Current Topics of Microbiology

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Humanizing bone marrow in immune-deficient mice2008

    • Author(s)
      Ando, K, et. al.
    • Journal Title

      Current Topics of Microbiology (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Humanizingz bone marrow in immune-deficient mice2008

    • Author(s)
      AndoK, et. al.
    • Journal Title

      Current Topics of Microbiology (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiopoietin-1 supports induction of hematopoietic activity in human CD34(-) bone marrow cells2007

    • Author(s)
      Nakamura Y, et. al.
    • Journal Title

      Experimental Hematology 35

      Pages: 1872-1883

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Two distinct stem cell lineages in murine bone marrow2007

    • Author(s)
      Koide Y, et. al.
    • Journal Title

      Stem Cells 25

      Pages: 1213-1221

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Gene expression profiles of endothelial progenitor cells by oligonuclotide microarray analysis2007

    • Author(s)
      Furukawa, et. al.
    • Journal Title

      Mol Cell Biochem 298

      Pages: 125-138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effect of coaching on physichological adjustment in patients with spinocerevellar degeneration A pilot study2007

    • Author(s)
      Izumi, et. al.
    • Journal Title

      Clinical Rehabilitation 21

      Pages: 987-996

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Preferential hypermethylation of the Dickkof-1 promoter in core-binding factor leukemia2007

    • Author(s)
      Suzuki R, et. al.
    • Journal Title

      Br J Hematol 138

      Pages: 624-631

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Angiopoietin-a supports induction of hematopoietic activity in human CD34(-) bone marrow cells2007

    • Author(s)
      Nakamura, Y, et. al.
    • Journal Title

      Experimental Hematology 35

      Pages: 1872-1883

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Two distinct stem cell lineages in murine bone marrow2007

    • Author(s)
      Koide, Y, et. al.
    • Journal Title

      Stem Cells 20

      Pages: 1213-1221

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of coaching on psychological adjustment in patients with spinocerebellar degeneration : A pilot study2007

    • Author(s)
      Izumi, S, et. al.
    • Journal Title

      Clinical Rehabilitation 21

      Pages: 987-996

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gene expression profiles of endothelial progenitor cells by ologonucleotide microarray analysis.2007

    • Author(s)
      Furuhata, S, et. al.
    • Journal Title

      Mol Cell Biochem 298

      Pages: 624-631

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Preferential hypermethylation of the Dickkopf-1 prompter in core-binding factor leukemia2007

    • Author(s)
      Suzuki, R, et. al.
    • Journal Title

      Br J Hematol 138

      Pages: 624-631

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Angiopoietin-1 supports induction of hematopoietic activity in human CD34(-) bone marrow cells2007

    • Author(s)
      NakamiuaY, et. al.
    • Journal Title

      Expermental Hematology 35

      Pages: 1872-1883

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two distnct stem cell lineages in muriIle bone marrow2007

    • Author(s)
      KoideY, et. al.
    • Journal Title

      Stem Cells 25

      Pages: 1213-1221

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two distinct stem cells lineages in murine bone marrow2007

    • Author(s)
      Koide, Y et al.
    • Journal Title

      Stem Cells (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment2006

    • Author(s)
      Muguruma, Y et al.
    • Journal Title

      Blood 107・5

      Pages: 1878-1887

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic cells2006

    • Author(s)
      Yahata, T et al.
    • Journal Title

      Blood 108・7

      Pages: 2446-2454

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression of CD90 on keratinocyte stem/progenitor cells2006

    • Author(s)
      Nakamura, Y et al.
    • Journal Title

      British Journal of Dermatology 154

      Pages: 1062-1070

    • Related Report
      2006 Annual Research Report
  • [Presentation] Human hematopoietic stem cell hhierarchy in bone marrow hematopioetic microenviroment2007

    • Author(s)
      Yahat T, et. al.
    • Organizer
      Stem cell symposium
    • Place of Presentation
      Awajishima
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Interactiion betweeromentn human hematopoietic stem cells and bone marrow hematopoietic microemviroment2007

    • Author(s)
      Yahata T, et. al.
    • Organizer
      Japanease Society of Hematology Meeting
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Exxpression of CD11c on cord blood CD34(-)hematopoietic stem cell2007

    • Author(s)
      Nakamura Y, et. al.
    • Organizer
      Japanease Society of Hematology Meeting
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] In vivo model for human red blood ce maturation analysis2007

    • Author(s)
      Mugauruma Y, et. al.
    • Organizer
      Japanease Society of Hematology Meeting
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Human hematopoietic stem cell hierarchy in bone marrow hematopoietic microenvironment2007

    • Author(s)
      Yahata, T, et. al.
    • Organizer
      Stem cell symposium
    • Place of Presentation
      Awajishima
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Interaction between human hematopoietic stem cells and bone marrow hematopoietic microenvironment2007

    • Author(s)
      Yahata, T, et. al.
    • Organizer
      Japanese Society of Hematology Meeting
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of CD11c on cord blood CD34(-) hematopoietic stem cells2007

    • Author(s)
      Nakamura, Y, et. al.
    • Organizer
      Japanese Society of Hematology Meeting
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] In vivo model for human red blood cell maturation analysis2007

    • Author(s)
      Muguruma, Y, et. al.
    • Organizer
      Japanese Society of Hematology Meeting
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒト造血幹細胞と骨髄内造血微小環境の相互作用2007

    • Author(s)
      八幡 崇, 他
    • Organizer
      日本血液学会総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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