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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
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2001: ¥8,500,000 (Direct Cost: ¥8,500,000)
KeywordsRegenerative medicine / Organogenesis / Generation of hematopoiesis / Yolk sac / AGM region / CD34 / Hematopoietic stem cell / Fetal therapy / 造血 / 全胚胎児培養 / 血管内皮細胞 / 二次造血 / 全胚培養 / B細胞 / OP9ストローマ細胞 / キメラ胎仔マウス
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.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (55 results)

All Other

All Publications (55 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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsui A: "gp130 and c-kit signals synergistically induce thrombopoietin production by hematopoietic cells"Int J Hematol. 72. 455-462 (2001)

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

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi T: "Surface protein D and KL-6 as serological indicators of Pneumocystis carinii preumonia in a child with acute lymphoblastic leukemia"J Med. 32. 41-51 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Xu M: "Evidence for the presence of primitive megakaryopoiesis in the early yolk sac"Blood. 97. 2016-2022 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ma F: "Development of human lymphohematopoietic stem/progenitor cells defined by CD34 and CD81 expressions"Blood. 97. 3755-3762 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyamoto K: "Inhibitory effect of interleukin-3 on the early development of human B-lymphopoiesis"Br J Haematol. 114. 690-697 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hisakawa H: "Human granulocyte-macrophage colony-stimulating factor(hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryo expressing hGM-CSF receptors but not erythropoietin"Blood. 98. 3618-3625 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuji K: "Expression of G-CSF receptor on myeloid progenitors"Leukemia & Lymphoma. 42. 1351-1357 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ma F: "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. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] 辻浩一郎: "Blackfan-Diamond症候群"小児科診療. 64. 188 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 辻浩一郎: "試験管内造血幹細胞増幅"現代医療. 33. 2011-2015 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 辻浩一郎: "造血幹細胞コロニー刺激因子と臍帯血造血幹細胞の対外増幅"日本産婦人科・新生児血液学会誌. 10. 33-36 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 浅野茂隆: "ES細胞を用いた組織再生の基礎"整形・災害外科. 44. 865-869 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 辻浩一郎: "造血幹細胞のex vivo増幅の現状"分子細胞療法2. 450-453 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 辻浩一郎: "造血幹細胞"小児科診療. 64. 2157-2162 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 辻浩一郎: "幹細胞を利用した再生医療"小児内科. 34. 37-41 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 辻浩一郎: "サイトカインを用いた造血幹細胞増幅"血液・腫瘍科. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] 辻浩一郎: "血液細胞の再生医学"ゲノム医学. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshimasu: "Prompt and durable hematopoietic reconstitution by an unrelated cord blood transplantation in a child with Fanconi anemia"

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuji K, Ueda T, Ebihara Y: "Methods in Molecular Medicine-Cytokines and Colony Stimulating Factor(Cytokine mediated expansion of human NOD/SCID-repopulating cells)"The Human Press(in press). (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 田中竜平, 辻浩一郎: "造血器疾患治療マニュアル"浅野茂隆、池田康夫、内田卓編、メディカルレビュー社(印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] 辻浩一郎: "必携造血幹細胞移植-わが国のエビデンスを中心に-"小寺良尚、加藤俊一編、医学書院(印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] 辻浩一郎: "小児白血病ハンドブッック"月本一郎編、中外医学社(印刷中).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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