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2002 Fiscal Year Final Research Report Summary

Analysis of the mechanism for organogenesis in mouse embryo and its application to therapeutic transplantation to human fetus

Research Project

Project/Area Number 13470157
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionThe University of Tokyo

Principal Investigator

TSUJI Kouichiro  The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (50179991)

Co-Investigator(Kenkyū-buntansha) EBIHARA Yasuhiro  The University of Tokyo, The Institute of Medical Science, Assistant, 医科学研究所, 助手 (40302608)
Project Period (FY) 2001 – 2002
KeywordsRegenerative medicine / Organogenesis / Generation of hematopoiesis / Yolk sac / AGM region / CD34 / Hematopoietic stem cell / Fetal therapy
Research Abstract

In this project, we indicated the following results according mouse embryonic hematopoiesis.
(1)In mouse embryogenesis, the primitive hematopoiesis in 7.5 days postcoitum (dpc) yolk sac (YS) has megakryocytopoiesis different from that of the definitive hematopoiesis in adult bone marrow.
(2)Stromal cells derived from aorta-gonad-mesonephros (AGM) region in 10.5 dpc mouse embryo can support the development of hematopoietic stem cells (HSC) in the definitive hematopoiesis.
(3)The Stromal cells from AGM region in 10.5 dpc mouse embryo can stimulate the generation of definitive hematopoiesis from not only AGM region but also YS at 8.0 dpc, a time when YS and embryo are not connected by blood vessels.
(4)8.25 dpc mouse YS was engrafted upon YS of donor embryo at the same stage to make YS-YS chimeric embryo. After the incubation of the chimeric embryo for 66 hours, we identified B cells originated from donor YS in the chimera, suggesting that a part of definitive hematopoiesis at least is generated from YS in mouse embryogenesis.
(5) The stromal cells are also capable of supporting the development of cord blood HSC derived from human fetal hematopopiesis.
(6) While CD34 is expressed on c-Kit+ HSC in mouse fetuses and neonates, the expression on HSC decreased with aging, and in mice older than 10 weeks, most of HSC are included in CD34-negative fraction.
These results are useful for the further development of regenerative medicine, and the analysis of mammalian organogenesis.

  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Matsuoka S., et al.: "CD34 expression on long-term repopulating hematopoietic stem cells changes during developmental stages."Blood. 97. 419-425 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi T., et al.: "Surface protein D and KL-6 as serological indicators of Pneumocystis carinii pneumonia in a child with acute lymphoblastic leukemia."J.Med.. 32. 41-51 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Xu M., et al.: "Evidence for the presence of primitive megakaryopoiesis in the early yolk sac."Blood. 97. 2016-2022 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshimasu T., et al.: "Prompt and durable hematopoietic reconstitution by an unrelated cord blood transplantation in a child with Fanconi anemia."Bone Marrow transplant.. 27. 767-769 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ma F., et al.: "Development of human lymphohematopoietic stem/progenitor cells defined by CD34 and CD81 expressions."Blood. 97. 3755-3762 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueda T., et al.: "Hematopoietic capability of cord blood CD34+ cells : a comparison with that of adult bone marrow CD34+ cells."Int.J.Hematol.. 73. 457-462 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyamoto K., et al.: "Inhibitory effect of interleukin-3 on the early development of human B-lymphopoiesis."Br.J.Haematol.. 114. 690-697 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hisakawa H., et al.: "Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryo expressing hGM-CSF receptors but not erythropoietin receptors."Blood. 98. 3618-3625 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuji K., et al.: "Expression of G-CSF receptor on myeloid progenitors."Leukemia & Lymphoma. 42. 1351-1357 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuoka S., et al.: "Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleura by aorta-gonad-mesonephros region-derived stromal cells."Blood. 98. 6-12 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ma F., et al.: "Growth of human T-cell acute lymphoblastic leukemia lymphoblasts in NOD/SCID fetal thymus organ culture : a possible role of the expression of IL-7 receptor in the proliferation of T-lymphoid leukemic cells."Leukemia. 16. 1541-1548 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshimasu T, et al.: "Successful treatment of relapsed blastic natural killer cell lymphoma with unrelated cord blood transplantation."Bone Marrow Transplant.. 30. 41-44 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito M., et al.: "NOD/SCID/gcnull mouse : A novel excellent recipient mouse for engraftment of human cells."Blood. 100. 3175-3182 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ebihara Y., et al.: "Reconstitution of human hematopoiesis in NOD/SCID mice by clonal cells expanded from single CD34+CD38- cells expressing Flk2/Flt3."Br.J.Haematol.. 119. 525-534 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuji K., et al.: "Development of human lymphohematopoiesis defined by CD34 and CD81 expressions."Leukemia & Lymphoma. 43. 2269-2273 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuji K., et al.: "Cytokine mediated expansion of human NOD/SCID-repopulating cells. Methods in Molecular Medicine-Cytokines and Colony Stimulating Factors."Korholz D and Kiess W (The Human Press, Totowa). 496 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuoka S, et al.: "CD34 expression on long-term repopulating hematopoietic stem cells changes during developmental stages"Blood. 97. 419-425 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi T, et al.: "Surface protein D and KL-6 as serological indicators of Pneumocystis carinii pneumonia in a child with acute lymphoblastic leukemia"J.Med. 32. 41-51 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Xu M, et al.: "Evidence for the presence of primitive megakaryopoiesis in the early yolk sac."Blood. 97. 2016-2022 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshimasu T, et al.: "Prompt and durable hematopoietic reconstitution by an unrelated cord blood transplantation in a child with Fanconi anemia"Bone Marrow Transplant. 27. 767-769 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ma F, et al.: "Development of human lymphohematopoietic stem progenitor cells defined by CD34 and CD81 expressions"Blood. 97. 3755-3762 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueda T, et al.: "Hematopoietic capability of cord blood CD34+ cells : a comparison with that of adult bone marrow CD34+ cells"Int.J.Hematol. 73. 457-462 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyamoto K, et al.: "Inhibitory effect of interleukin-3 on the early development of human B-lymphopoiesis"Br.J.Haematol. 114. 690-697 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hisakawa H, et al.: "Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryo expressing hGM-CSF receptors but not erythropoietin receptors"Blood. 98. 3618-3625 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuji K, et al.: "Expression of G-CSF receptor on myeloid progenitors"Leukemia & Lymphoma. 42. 1351-1357 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuoka S, et al.: "Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleura by aorta-gonad-mesonephros region-derived stromal cells"Blood. 98. 6-12 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ma F, et al.: "Growth of human T-cell acute lymphoblastic leukemia lymphoblasts in NOD/SCID fetal thymus organ culture : a possible role of the expression of IL-7 receptor in the proliferation of T-lymphoid leukemic cells."Leukemia. 16. 1541-1548 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshimasu T, et al.: "Successful treatment of relapsed blastic natural killer cell lymphoma with unrelated cord blood transplantation"Bone Marrow Transplant. 30. 41-44 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito M, et al.: "NOD/SCID gcnull mouse: A novel excellent recipient mouse for engraftment of human cells"Blood. 100. 3175-3182 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ebihara Y, et al.: "Reconstitution of human hematopoietis in NOD/SCID mice by clonal cells expanded from single CD34+CD38-cells expressing Flk2/Flt3"Br J Haematol. 119. 525-534 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuji K, et al.: "Development of human lymphohematopoiesis defined by CD34 and CD81 expressions"Leukemia & Lymphoma. 43. 2269-2273 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuji K, et al.: "Cytokine mediated expansion of human NOD/SCID-repopulating cells"Methods in Molecular Medicine-Cytokines and Colony Stimulating Factors. (edited by Korholz D and Kiess w) (The Human Press, Totowa). (2002)

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

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Published: 2005-04-19  

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