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The mechanisms of proliferation and differentiation of hematopoietic multipotent stem cells.

Research Project

Project/Area Number 01570542
Research Category

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

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionYokohama City University, School of Medicine

Principal Investigator

SASAKI Hideki  Yokohama City Univ. School of Medicine, Pediatrics, Associate Professor, 医学部, 助教授 (50106316)

Co-Investigator(Kenkyū-buntansha) INOUE Tohru  Yokohama City Univ. School of Medicine, Pathology, Associate Professor, 医学部, 助教授 (50100110)
MATSUYAMA Shusuke  Yokohama City Univ. School of Medicine, Pediatrics, Professor, 医学部, 教授 (20045983)
IKUTA Koichiro  Yokohama City Univ. School of Medicine, Pediatrics, Assistant Professor, 医学部, 講師 (80159590)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
KeywordsHemopoietic Stem Cells / Interleukin / Interleukin 6 / Stem Cell Factor / Leukemia Inhibitory Factor / Erythropoietin / インタ-ロイキン3 / インタ-ロイキン6 / 白血病阻害因子 / 幹細胞増殖因子 / 老化 / 免疫磁気ビ-ズ / CD_<34>
Research Abstract

To clarify tlie mechanisms of proliferation and differentiation of multipotent hemopoietic stem cells, we investigated the effects of IL-3, IL-6, SCF, LIF and EPO on early appearing CFU-S(CFU-S_8)and late appearing CFU-S(CFU-S_<12>)in short-term suspension culture. We also employed the ^3H-TdR suicide method to test whether the modulation of CFU-S by IL-3 and EPO involved the proliferative process. A single addition of IL-3 or SCF increased the numbers of both subpopulation of CFU-S recovered in culture with dose-dependent fashion, while EPO, at least up to 10u/ml, increased solely CFU-S_8. Further, dose-response curves of CFU-S_8 and CFU-S_<12> to IL-3 and SCF were different, which confirmed the speculation that CFU-S_8 and CFU-S_<12> are relatively different subpopulation. Our results including ^3H-TdR suicide suggested that EPO acted on both of CFU-S_8 and CFU-S_<12> to stimulate proliferation with differentiation into more mature population in erythroi. d lineage, and that IL-3 acted not only on these two subpopulation but also on more primitive stem cell population which was resistant to 5FU. The investigation on ihe action of SCF in detail is on going. Another two cytokines, IL-6 and LIF, showed synergistic stimulating activity with IL--3. The physiological roles of these factors in the regulatory mechanisms of stem cell proliferation are still unknown. However, studies of tlie action of these cytokines on hemopoietic stem cells are important research fields in regarding to clinical uses such as in votro expansion for transplantation.
Human BFU-E, CFU-GM, and CFIJ-Mix were 20x enriched by one-step immunomagnetic beads separation using anti-CD_<34> antibody. Basical studies suggested multi-step separation procedures should be required for further improvement of the efficiency for clinical use.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] 佐々木 秀樹他: "免疫磁気ビ-ズを用いた造血前駆細胞の濃縮" Immunohaematology. 12. 91-95 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 井上 達他: "Hemopoietic stem cell growth and microenvironment of the senescent mice." J.Experimental Hematology. 17. 602 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 井上 達他: "造血幹細胞の病理ー多能性幹細胞をめぐる新知見と問題点ー" 横浜医学. 42. 153-176 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 佐々木 秀樹他: "Enrichment of hemopoietic progenitor cells in cord blood and in peripheral blood by immunomagnetic beads." Int.J.of Hematology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 佐々木 秀樹他: "The effects of ILー3,SCF and erythropoietin on CFUーS in shortーterm culture" J.Experimental Hematology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Inoue, Y. Hirabayashi, H. Sasaki, H. Kuramoto, S. Matsuyama, M. Kanisawa: "Hemopoietic stem cell growth and microenvironment of the senescent mice." J. Experimental Hematology. 17. 602 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Sasaki and S. Matsuyama: "Enrichment of human hemopoietic progenitor cells by immunomagnetic beads separation." Immunohaematology. 12. 91-95 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Inoue, Y. Hirabayashi, T. Iwasawa, H. Sasaki, M. Umeda: "Pathology of hemopoietic stem cells - New concept on pluripotent stem cell compartment and future prospects for research -" Yokohama Medical Journal. 42. 153-176 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Sasaki, K. Ikuta, Y. Kajigaya, S. Kai, H. Sekiguchi, H. Takahashi S. Matsuyama: "Enrichment of hemopoietic progenitor cells in cord blood and in peripheral blood by immunomagnetic beads."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Sasaki, T. Inoue, Y. Hirabayashi, S. Matsuyama: "The effects of IL-3, SCF and erythropoietin on CFU-S in shortterm culture."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 佐々木 秀樹 他: "免疫磁気ビ-ズを用いた造血前駆細胞の濃縮" Immunohaematology. 12. 91-95 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 井上 達他: "Hemopoietic stem cell growth and microenvironment of the senescent mice." J.Experimental Hematology. 17. 602 (1989)

    • Related Report
      1991 Annual Research Report
  • [Publications] 井上 達他: "造血幹細胞の病理ー多能性幹細胞をめぐる新知見と問題点ー" 横浜医学. 42. 153-176 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 佐々木 秀樹他: "Enrichment of hemopoietic progenitor cells in cord blood and in peripheral blood by immunomagnetic beads." In・preparation for Int.J.of Hematology.

    • Related Report
      1991 Annual Research Report
  • [Publications] 佐々木 秀樹 他: "The effects of ILー3,SCF and erythropoietin on CFUーS in shortーterm culture." In preparation for J.Experimental Hematology.

    • Related Report
      1991 Annual Research Report
  • [Publications] 佐々木 秀樹,他: "免疫磁気ビ-ズを用いた造血前駆細胞の濃縮" Immunohaematology. 12. 91-95 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Inue,H.Sasaki,et al.: "Hemopoietic stem cell growth and microenvironment of the senescent mice." J.Experimental Hematology. 17. 602- (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] 井上 達,佐々木 秀樹,他: "造血幹細胞の病理:多能性幹細胞をめぐる新知見と問題点" 横浜医学.

    • Related Report
      1990 Annual Research Report
  • [Publications] 佐々木秀樹: "免疫磁気ビ-ズを用いた造血前駆細胞の濃縮" Immunohaematology. 12. 91-95 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 井上達: "Hemopoietic stem cell growth and microenvi-ronment of the senescent mice." J.Experimental Hematology. 17. 602 (1989)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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