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2004 Fiscal Year Final Research Report Summary

Human hematopoietic reconstitution bu a single hematopoietic stem cell using intra-bone marrow transplantation

Research Project

Project/Area Number 15609006
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 幹細胞生物学
Research InstitutionTOKAI UNIVERSITY

Principal Investigator

ANDO Kiyoshi  Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (70176014)

Co-Investigator(Kenkyū-buntansha) KAWADA Hiroshi  Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (20276801)
Project Period (FY) 2003 – 2004
KeywordsHematopoietic stem cell / Immunodeficient mice / Intra-bone marrow transplantation
Research Abstract

To measure the ability of human hematopoietic stem cells (HSCs), SCID-repopulating cell (SRC) assay has been widely used, in which human HSCs are transplanted into NOD/SCID mouse. However, when human cells are transferred from a tail vein, cells must go through various obstacles until they reach the mouse marrow environment, which could explain the generally low homing efficiency in this system. Thus, the capability of HSCs may be underestimated by this intravenous (iv) transplantation method. In our attempt to reveal true SRC potential to self-renew and differentiate into multi-lineage mature cells in bone marrow, we introduced cells into mouse marrow directly (intra-bone marrow [iBM]) to minimize the effect of factors, which may prevent homing of HSCs, and compared the frequency of SRCs measured by the two method. When cord blood CD34^+CD38^- cells were transplanted in NOD/SCID mice by iBM, a 15-fold higher frequency of SRC, 1. in 44 CD34^+CD38^- cells, was achieved compared with 1 i … More n 660 by iv. Furthermore, the iBM transplant showed high levels of engraftment in the secondary transplantation. Our results indicate that the iBM injection strategy is more sensitive and direct way to measure the capability of human SRCs and is useful to investigate the interaction of HSCs and marrow environment in vivo.
Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. However, the responsible BM cells have not been fully identified. Here, we used two independent clonal studies to determine the origin of bone marrow (BM)-derived cardiomyocytes. First, we transplanted single CD34^-c-kit^+Sca-1^+lineage^- side population (CD34^-KSL-SP) cells or whole BM cells from mice ubiquitously expressing enhanced green fluorescent protein (EGFP) into lethally-irradiated mice, induced myocardial infarction (MI), and treated the animals with G-CSF to mobilize stem cells to the damaged myocardium. At 8 weeks post-MI, from 100 specimens we counted only 3 EGFP^+actinin^+ cells in myocardium of CD34^-KSL-SP cells-transplanted mice, but more than 5,000 EGFP^+ actinin^+ cells in whole BM cell-transplanted mice, suggesting that most of EGFP^+actinin^+ cells derived from non-hematopoietic BM cells. Next, clonally purified non-hematopoietic mesenchymal stem cells (MSC), CMG cells, that expressed EGFP in the cardiomyocyte-specific manner were transplanted directly into BM of lethally-irradiated mice, MI was induced, and they were treated with G-CSF. EGFP^+actinin^+ cells were observed in the ischemic myocardium, indicating that CMG cells had been mobilized and differentiated into cardiomyocytes. Together, these results suggest that the origin of the vast majority of BM-derived cardiomyocytes is MSC. Less

  • Research Products

    (16 results)

All 2005 2004 2003

All Journal Article (16 results)

  • [Journal Article] The Poetntial and origin of hematopoietic population in human skeletal muscle.2005

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

      Leukemica Res 29

      Pages: 317-324

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The poetnial and origin of hematopoietic in human skeletal muscle.2005

    • Journal Title

      Leukemica Res 29

      Pages: 317-324

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Non-hematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction.2004

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

      Blood 104

      Pages: 3581-3587

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Competitive repopulation assay from two cord blood units of CD34+ cells in NOD/SCID/genull mice.2004

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

      Molecular Therapy 10

      Pages: 882-891

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Non-hematopoietic mesenchymal stem cell can be mobilized and differentiate into cardiomyocytes after myocardial infarction.2004

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

      Blood 104

      Pages: 3581-3587

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Competitive repopulation assay from two cord blood unite of CD34+ cells in NOD/SCID/ gcnull mice.2004

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

      Molecular Therapy 10

      Pages: 882-891

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A highly sensitive strategy for scid-repopulating cell assay by direct injection of primitive human hematopoietic cells into NOD/SCID mice bone marrow.2003

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

      Blood 101

      Pages: 2905-2913

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Scrum stem cell growth factor (SCGF) for monitoring hematopoietic recovery following stem cell transplantation (SCT).2003

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

      Bone Marrow Transplantation 32

      Pages: 391-398

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] In vivo and in vitro differentiation of myocytes from human bone marrow-derived multipotent progenitor cells.2003

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

      Exp Hematol. 31

      Pages: 1323-1330

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Biodegradable Gelatin Hydrogel Potentiates the Angiogenic Effect of GF4 Plasmid in Rabbit Hindlimb Ischemia.2003

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

      J Am Coll Cardiol 41

      Pages: 1056-1062

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] CD5+ B cells (B1 cells) develop predominantly in the spleen of NOD/SCOD/genull (NOG) mice transplanted with human umbilical cord blood, bone marrow and mobilized peripheral blood CD34+cells.2003

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

      Exp Hematol. 31

      Pages: 789-797

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Transplantation of Mesenchymal Stem Cell Embedded in Atelocollgen Gel to the Intervertebral Disc : A Potential Therapeutic Model for Disc Degeneration.2003

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

      Biomaterials 24

      Pages: 6561-6541

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A highly sensitive strategy for scid-repopulationg cell assay by Direct injection human hematopoietic cells into NOD/SCID mice Bone marrow.2003

    • Journal Title

      Blood 101

      Pages: 2905-2913

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Serum stem cell growth factor (SCGF) for monitoring hematopoietic Recover following stem cell trans plantation (SCT).2003

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

      Bone Marrow Transplantation 32

      Pages: 391-398

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] CD5+ B cells (B1 cells) develop predominantly in the spleen of NOD/SCOD/gcnull (NOG) mice transplanted with human umbilical cord blood, bone marrow and mobilized peripheral blood CD34+cells.2003

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

      Exp Hematol. 31

      Pages: 489-797

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Transplantation of Mesenchymal Stem Cell Embedded in Atelocollgen Gel to the Intervertebral Disc: A Potential Therapeutic Model for Disc Degeneration.2003

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

      Biomaterials 24

      Pages: 6561-6541

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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