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1994 Fiscal Year Final Research Report Summary

SELF-RENEWAL AND COMMITTMENT OF PURIFIED HUMAN STEM CELLS : REGULATION BY ONCOGENES AND CYTOKINES

Research Project

Project/Area Number 05454334
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionKYOTO PREFECTURAL UNIVERSITY OF MEDICINE

Principal Investigator

SONODA Yoshiaki  KYOTO PREFECTURAL UNIVERSITY OF MEDICINE DEPARTMENT : DEPARTMENT OF HYGIENE POSITION : ASSOCIATE PROFESSOR, 医学部, 助教授 (60206688)

Co-Investigator(Kenkyū-buntansha) YOKOTA Syouhei  KYOTO PREFECTURAL UNIVERSITY OF MEDICINE DEPARTMENT : DEPARTMENT OF THIRD INTERN, 医学部, 助手 (80231687)
Project Period (FY) 1993 – 1994
Keywordshematopoietic stem cell / FACS / c-kit / SCF / flt3 / flk2 ligand / IL-4 / CD34 / antisense DNA
Research Abstract

First, we have purified CD34^+ Cells from bone marrow (BM), peripheral blood (PB) and cord blood (CB) using immunological staining and cell sorting. Based on the expression levels of CD33, CD38, HLA-DR,and c-kit, CD34^+ cells could be subdivided into several populations which represent different stage of differentiation. Then, the interactions between ligands for receptor type tyrosine kinases such as c-kit or flt3 and various cytokines including IL-3, GM-CSF,G-CSF,Epo, IL-9, IL-6, and IL-4 have been extensively studied.
The interactions between these cytokines found in this study are as follows : (1) Until now, IL-3, GM-CSF,SCF,and IL-9 are known as burst-promoting activity (BPA). SCF showed a distinct BPA on CD34^+C-kit^<high> cells, whereas its BPA effect became much weaker when CD34^+C-kit^<low> cells were used as a target. In contrast, IL-9 alone failed to show BPA on CD34^+C-kit^<low> cells. SCF showed distinct synergistic actions with GM-CSF and IL-9 in support of erythroid burst … More and/or mixed colony formation. (2) SCF can synergize with G-CSF in support of neutrophil colony formation. SCF showed a distinct synergistic action with IL-4 in neutrophil colony formation when CD34^+c-kit^<low or -> cells were used as targets. (3) IL-4 showed a distinct BPA on CD34^+c-kit^<low> cells. In addition, IL-4 synergized with SCF in support of mixed colony formation. (4) FL did synergize with G-CSF in support of neutrophil colony formation. FL also synergized with IL-3 or GM-CSF in support of mixed colony formation in the presence of Epo. (5) Based on these data, we propose that IL-4 may affect the signal transduction pathways for c-kit/SCF and flt3/FL systems. (6) We established the method which enables large scale production and purification of phosphorothioate type anti-sense oligonucleotides. Antisense TGFbeta induced a increased colony forming ability on CD34^+c-kit^<low> cells, suggesting the release of non-cycling immature o Stem cells into active cell cycle.
We plan to investigate the molecular mechanisms which may explain the cytokine networks we found. Application of antisense DNA technology and differential display PCR method will provide an insight into the cellular basis of hematopoiesis. Less

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Sonoda Y et al.: "Human interleukin-4 inhibits proliferation of megakaryocyte progenitor cells in culture." Blood. 81. 624-630 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda Y at al.: "Multilineage response in aplastic anemia patients following long-term administra---" STEM CELLS. 11. 543-554 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda Y et al.: "Interleukin-6 supports terminal prolife-ration and maturation of human bone marrow--" J Kyoto Pref Univ Med. 102. 873-883 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda Y et al.: "Interleukin-4-a dual regulatory factor in hematopoiesis." Leukemia and Lymphoma. 14. 231-240 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda Y et al.: "Synergistic actions of stem cell factor and other burst-promoting activities on---" Blood. 84. 4099-4106 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田精昭: "インターロイキン9(IL-9)" 臨床免疫. 27(Suppl16). 86-96 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田精昭: "末梢血幹細胞移植-基礎から臨床まで-" 南江堂(印刷中), (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 薗田精昭 他: "がん治療のあゆみ" 癌と化学療法社, 9 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda Y et al.: "Human interleukin-4 inhibits proliferation of megakaryocyte progenitor cells in culture." Blood. 81. 624-630 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sonoda Y et al.: "Multilineage response in aplastic anemia patients following long-term administration of filgrastim (recombinant human granulocyte colony stimulating factor)." STEM CELLS. 11. 543-554 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sonoda Y et al.: "Interleukin-6 supports terminal proliferation and maturation of human bone marrow derived mega-karyocyte progenitors in vitro." J Kyoto Pref Univ Med. 102. 873-883 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sonoda Y.: "Interleukin-4-a dual regulatory factor in hematopoiesis." Leukemia and Lymphoma. 14. 231-240 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sonoda Y et al.: "Synergistic actions of stem cell factor and other burst-promoting activities on proliferation of CD34+ highly purified blood progenitors expressing HLA-DR or different levels of c-kit protein." Blood. 84. 4099-4106 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sonoda Y.: "Interleukin-9 (IL-9)." Clinical Immunology. 27 (suppl.16). 86-96 (1995)

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

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Published: 1996-04-15  

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