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サイトカイン受容体の解析とそのヒト造血幹細胞の純化、増幅法への応用

Research Project

Project/Area Number 11770400
Research Category

Grant-in-Aid for Encouragement of Young Scientists (A)

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

Principal Investigator

海老原 康博  東京大学, 医科学研究所, 教務職員 (40302608)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsFlt3 / CD34 / 造血幹細胞 / NOD / SCIDマウス / 臍帯血 / G-CSF受容体 / 骨髄球系前駆細胞
Research Abstract

受容体型チロシンキナーゼファミリーに属しているflt3とそのLigand(FL)が最近同定され、その造血系に対する作用が注目されている。本研究では、Flt3のヒト臍帯血CD34陽性細胞における発現を解析し、Flk2陽性、陰性細胞を各々FACSソーティングし造血能を比較検討した。CD34陽性細胞の81.3±8.0%にFlt3の発現が認められ、CD34+CD33+細胞の85.2±4.0%、CD34+CD33-細胞の75.3±4.2%、CD34+CD38+細胞の77.4±4.5%、CD34+CD38-細胞の80.4±4.8%に認められた。コロニーアッセイからは、大部分の骨髄球系前駆細胞はFlt3を発現しているが、赤血球系前駆細胞や多能性造血前駆細胞にはFlt3発現細胞と非発現細胞が存在することが示された。しかし、CD34+Flt3+細胞から形成された混合コロニーは、CD34+Flt3-細胞由来のものと比較して大型のコロニーが多数認められたことより、より未分化な多能性造血前駆細胞はFlk2を発現している可能性が示唆された。次に、CD34+Flt3+細胞、CD34+Flt3-細胞をそれぞれ10000個ずつNOD/SCIDマウスに移植すると、CD34+Flt3+細胞からのみリンパ球、骨髄球、種々の造血前駆細胞を含む造血再構築能が認めれた。より未分化なlin-CD34+CD38-細胞中のFlt3陽性細胞を単一細胞に分離し、SCF+FL+TPO+IL-6+可溶性IL-6受容体存在下で1-2週間液体培養した後、増殖が認められたクローンについて、NOD/SCIDマウスに移植して造血再構築能を検討すると、16匹のNOD/SCIDマウスのうち6匹37.5%でヒト造血再構築が確認された。
以上の結果より、ヒト造血再構築能を有する造血幹細胞はFlt3を発現していることが示された。

Report

(2 results)
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Ebihara Y.: "Exclusive expression of G-CSF receptor on myeloid progenitors in bone marrow CD34+ cells."Br.J.Haematol. 109. 153-161 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueda T.: "Expansion of human NOD/SCID-repopulating cells by stem cell factor, Flk2/Flt3 ligand, thrombopoietin, IL-6 and soluble IL-6 receptor."J.Clin.Invest.. 105. 1013-1021 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueda T.: "Hematopoietic repopulating ability of cord blood CD34+ cells in NOD/Shi-scid mice."Stem Cells. 18. 204-213 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueda T.: "Massive pericardial and pleural effusion with anasarca following allogenic bone marrow transplantation."Int.J.Hematol. 71. 394-397 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishii T.: "Improvement in bronchiolitis obliterans organizing pneumonia by combination of oral prednisolone and low dose erythromycin in a child after allogenic bone marrow transplantation."Bone Marrow Transplant.. 26. 907-911 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshino H.: "Natural killer cell depletion by anti-asialo GMl antiserum treatment enhances human hematopoietic stem cell engraftment in NOD/Shi-scid mice."Bone Marrow Transplant.. 26. 1211-1216 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takaki S.: "Control of B cell production by the adaptor protein Lnk Definition of a conserved family of signal-modulating proteins."Immunity. 13. 599-609 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsuoka S.: "CD34 expression on long-term repopulation hematopoietic stem cells changes during developmental stages."Blood. 97. 419-425 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xu M.: "Evidence for the presence of primitive megkaryopoiesis in early yolk sac."Blood. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueda T.: "Hemsatopoietic capability of cord blood CD34+ cells ; a comparison with that of adult bnone marrow CD34+ cells."Int.J.Hematol.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Ebihara Y.: "LTC-IC on human hematopoiesis."Hematology & Oncology (in Japanese). 40 suppl. 88-95 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishii T.: "L-asparaginase-induced necrotizing acute pancreatitis in the late phase of treatment for acute lymphoblastic leukemia : A case report."Japan J.Pediatr Hematol.(in Japanese). 14. 328-332 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ebihara Y: "Exclusive expression of G-CSF receptor on myeloid progenitors in bone marrow CD34^+ cells"Br J Haematol. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuoka S: "CD34 expression on long-term repopulating hematopoietic stem cells changes during developmental stages"Blood. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueda T: "Expansion of human NOD/SCID-repopulating cells by stem cell factor, Flk2/Flt3 ligand, thrombopoietin, interleukin-6 and soluble interleukin-6 reseptor"J.Clin.Invest. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishii T: "Expression of SDF-1/PBSF reseptor CXCR4 on CD34^+ human bone marrow cells in a phenotypic alteration for commited lymphoid progenitors"J Immunol. 163. 3612-3620 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sui X: "Soluble IL-6 receptor with IL-6 stimulates megakaryopoiesis from human CD34^+ cells through gp130 signaling"Blood. 93. 2525-2532 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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