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Isolation concentration, and preservation of hemopoietic stem cells and its clinical

Research Project

Project/Area Number 01440049
Research Category

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

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionJichi Medical School

Principal Investigator

MIURA Yasusada  Department of Medicine, JIchi Medical School, Professor, 医学部, 教授 (60048965)

Co-Investigator(Kenkyū-buntansha) IMAGAWA Shigehiko  Jichi Medi. School, Dept. Medi., Assistant, 医学部, 助手 (60231164)
MIWA Akiyoshi  Jichi Medi. School, Dept. Medi., Assistant Prof., 医学部, 講師 (40200224)
MUROI Kazuo  Jichi Medi. School, Dept. Medi., Assistant, 医学部, 助手 (50190939)
KOMATSU Norio  Jichi Medi. School, Dept, Medi., Assistant, 医学部, 助手 (50186798)
SUDA Toshio  Jichi Medi. School, Dept. Medi., Associate Prof., 医学部, 助教授 (60118453)
畠 清彦  自治医科大学, 医学部, 講師 (80192699)
倉田 寛一  自治医科大学, 医学部, 助手 (90215038)
高木 省治郎  自治医科大学, 医学部, 講師 (20158992)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥29,100,000 (Direct Cost: ¥29,100,000)
Fiscal Year 1991: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1990: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1989: ¥19,300,000 (Direct Cost: ¥19,300,000)
Keywordshemopoietic stem cells / hemopoietic growth factors / monoclonal antibody / CD34 / c-kit / mucopolysaccharide / spleen colony / anti-leukemic cell antibody / cーkit / WGA / CD33 / DIF / 破骨細胞
Research Abstract

The purpose of this research is to sort out and concentrate hemopoietic stem cells, which is only a minor population of hemopoietic tissue, to study their reactivity to growth factors, and finally to investigate the clinical applications.
The main results are as follows :
1) We sorted CD34^+CD33^- cell fraction from normal human bone marrow cells by a fluorescence activated cell sortor (FACS), which contain the most primitive stem cells. After treating these cells with IL-3, they turned into CD34^- CD33^+ cells and then were induced to mature blood cells by the addition of lineage specific cytokines such as IL-5 and G-CSF.
2) Murine hemopoietic cells were sorted by various monoclonal antibodies using a FACS. The c-kit^+, SCA-1^+ lineage^- cells were found to contain highly enriched primitive stem cells. They could reconstitute murine hemopoiesis when injected into lethally irradiated mice.
3) Sorted stem cells were of middle-size with round, immature nuclei and basophilic cytoplasm occasionally with some granules.
4) We established a riiegakaryocytic cell line, UT-7, which is completely dependent on various cytokines such as IL-3, GM-CSF, erythropoietin or IL-6. We investigated the appearance of erythropoietin receptors and followed the signal transduction pathways. A mucopolysaccharide was extracted and purified from this cell line cells, which induced the "differentiation" of original UT-7 cells when added in vitro.
5) Several anti-sugar chain monoclonal antibody were became available. Some of them were shown to recognize human leukemic cells, but not the normal sorted stem cells. This phenomenon could be applied on the purging of leukemic cells from patient bone marrow at the time of autologous bone marrow transplantation.
As a conclusion, our research projects yielded many valuable results published in leading international journals, and could be useful for both basic and clinical study on the hemopoiesis.

Report

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

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Suda,T.Okada,S.,Suda,J.,Miura,Y.,et al.: "A stimulatory effect of recombinant murine interleukin-7(IL-7)on-B-cell colony formation and inhibitory effect of IL-1 α." Blood. 74. 1936-1941 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ema,H.,Suda,T.,Miura,Y.,Nakauchi,H.: "Colony formation of clone-sorted human hematopoietic progenitors." Blood. 75. 1941-1946 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Gunji,Y.: "Support of early B-cell differentiation in mouse fetal liver by stromal cells and interleukin-7." Blood. 77. 2612-2617 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Komatsu.,N.: "Establishment and characterization of a human leukemic cell line with megakaryocytic features:Dependency on granulocyte-macrophage for colony-stimulating factor,interleukin 3,or erythropoietin growth and survival." Cancer Research. 51. 341-348 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Okada,S.,Nakauchi,H.,Nagayoshi,K.,Nishikawa,S.,Nishikawa,S.,Miura,Y.Suda,T.: "Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule." Blood. 78. 1706-1712 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Muroi,K.,Suda,T.,Nojiri,T.,Ema,H.,Amemiya,Y.,Miura,Y.,Hakomori,S.,et al.: "Reactivityprofiles of leukemic myeloblasts with monoclonal antibodies directed to sialosyl-Le^x and other lacto-series type 2 chain antigens:Absence of reactivity with normal hematopoietic progenitor cells." Blood. 79. 713-719 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Miura,Y.,Komatsu,N.,Suda,T.: "(Molecular biology and differentiation of megakaryocytes)Growth and differentiation of two human megakaryoblastic cell lines;CMK and UT-7." Wiley-Liss,New York, 12 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Miura,Y.: "(Myelodysplastic Syndrome and Cytokines)Differentiation pathways of clone-sorted CD34-positive cells." Elsevier Science Publishers, 39-48 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Suda, T. Okada, S., Suda, J., Miura, Y., et al.: "A stimulatory effect of recombinant murine interleukin-7 (IL-7) on B-cell colony formation and inhibitory effect of IL-1 alpha." Blood. 74. 1936-1941 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ema, H., Suda, T., Miura, Y., Nakauchi, H.: "Colony formation of clone-sorted human hematopoietic progenitors." Blood. 75. 1941-1946 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Gunji, Y.: "Support of early B-cell differentiation in mouse fetal liver by stromal cells and interleukin-7." Blood. 77. 2612-2617 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Komatsu, . N.: "Establishment and characterization of a human leukemic cell line with megakaryocytic features : Dependency on granulocyte-macrophage colony-stimulating factor, interleukin 3, or erythropoietin for growth and survival." Cancer Research. 51. 341-348 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Okada, S., Nakauchi, H.: "Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule." Blood. 78. 1706-1712 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Muroi, K., Suda, T.: "Reactivity profiles of leukemic myeloblasts with monoclonal antibodies directed to sialosyl-Le^x and other lacto-series type 2 chain antigens : Absence of reactivity with normal hematopoietic progenitor cells." Blood. 79. 713-719 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Miura, Y., Komatsu, N., Suda, T.: "Growth and differentiation of two human megakaryoblastic cell lines ; CMK and UT-7." Molecular biology and differentiation of megakaryocytes. Wiley-Liss. (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Miura, Y.: "Differentiation pathways of clone-sorted CD34-positive cells." Myelodysplastic Syndrome and Cytokines. Elsevier Science Publishers. (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamaguchi,T.: "Analysis of the survival of mature human eosinophils:Interleukinー5 prevents apoptosis in mature human eosinophils." Blood. 78. 2542-2547 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Honma,Y.: "Induction by some protein kinase inhibitors of differentiation of a mouse megakaryoblastic cell line established by coinfection with abelson murine leukemia virus and recombinant SV40 retrovirus." Cancer Research. 51. 4649-4655 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ohsaka,A.: "Enhanced neutrophil functions in a patient with colonystimulating activityーproducing Iung cancer." Journal of Internal Medicine. 230. 459-462 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Gunji,Y.: "Support of early Bーcell differentiation in mouse fetal liver by stromal cells and interleukinー7." Blood. 77. 2612-2617 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tsunoda,J.: "In vivo stem cell function of interleukinー3ーinduced blast cells." Blood. 78. 318-322 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tanaka,T.: "Stimulatory effects of granulocyte colonyーstimulating factor on Colony ーforming unitsーspleen(CFUーS)differentiation and PreーCFUーS proliferation in mice" Blood. 77. 2597-2602 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ohara,A.: "Generation of B lymphocytes from a Single hemopoietic progenitor cell in vitro." International Immunology. 3. 703-709 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nakauchi,H.: "In vitro single cell assay for human stem cells using facs cloneーsorting." Flow cytometry and image analysis for clinical applications. 227-232 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ema,H.: "Multipotent and committed CD34^+ cells in bone marrow transplantation." Jpn.J.Cancer Res.82. 547-552 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Miura,Y.: "Differentiation pathways of cloneーsorted CD34ーpositive cells." Myelodysplastic Syndrome and Cytokines. 39-48 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Komatsu,.N.: "Establishment and characterization of a human leukemic cell line with megakaryocytic features:Dependency on granulocyteーmacrophage colonyーstimulating factor,interleukin3,or erythropoietin for growth and survival." Cancer Research. 51. 341-348 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Okada,S.: "Effects of interleukin 3,interleukin 6,and granulocyte colonyーstimulating factor on sorted murine splenic progenitor cells." Exp.Hematol.19. 42-46 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ema,H.,Suda,T.,Miura,Y.,Nakauchi,H.: "Colony formation of cloneーsorted human hematopoietic progenitors." Blood. 75. 1941-1946 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Suda,T.,Ohara,A.,Suda,J.,Okada,S.,Tokuyama,N.,Miura,Y.: "Early B cell differentiation from hematopoietic stem cells in the presence of stromal cells and interleukinー7 (ILー7)." “Experimental Hematology Todayー1989"Gorin NC,Douay L (eds) springerーVerlag,New York,USA. 45-52 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yamaguchi,Y.,Suda,T.,Suda,J.,Eguchi,M.,Miura,Y.,Mita,S.,Hitoshi Y.,Tominaga,A.,Takatsu,K.: "Analysis of eosinophilーpredominant colonies formed by human hemopoietic precursor cells in the presence of purified interleukinー5." Acta Haematologica Japonica. 53. 688-698 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yamaguchi,Y.,Matsui,T.,Kasahara,T.,Etoh,S.,Takatsu,K.,Miura,Y.,Suda,T.: "In vivo changes of hemopoietic progenitors and the expression of the interleukin 5 gene in eosinophilic mice infected with toxocara canis." Exp.Hematol.18. 1152-1157 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ema,H.,Suda,T.,Nagayoshi,K.,Miura,Y.,Civin,C.I.,Nakauchi,H.: "Target cells for granulocyte colonyーstimulating factor,interleukinー3,and interleukinー5 in differentiation pathways of neutrophils and eosinophils." Blood. 76. 1956-1961 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Okada,S.,Suda,T.,Tokuyama,N.,Nagayoshi,K.Miura,Y.,Nakauchi,H.: "Effects of interleukin 3,interleukin 6,and granulocyte colonyーstimulating factor on sorted murine splenic progenitor cells." Exp.Hematol.19. 42-46 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Miura,Y.,Komatsu,N.,Suda,T.: "(Molecular biology and differentiation of megakaryocytes) Growth and differentiation of two human megakaryoblastic cell lines;CMK and UTー7" WileyーLiss,New York, 12 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 三浦 恭定編: "造血因子研究の潮流" 中外医学社, 272 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Komatsu,N.,Suda,T.,Moroi,M.,Tokuyama,N.,Sakata,Y.,Okada,M.,Miura,Y.,et al.: "Growth and differentiation of a human megakaryoblastic cell line,CMK." Blood. 74. 42-48 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Ema,H.,Suda,T.,Sakamoto,S.,Tomonaga,T.,Tsunoda,J.,Muroi,K.,Miura,Y.,et al.: "Effects of the in vivo administration of recombinant human granulocyte colony-stimulating factor following cytotoxic chemotherapy on granulocytic precursors in patients with malignant lymphoma." Jpn.J.Cancer Res.80. 577-582 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kurihara,N.,Suda,T.,Miura,Y.,Nakauchi,H.,Kodama,H.,Hiura,K.,et al.: "Generation of osteoclasts from isolated hematopoietic progenitor cells." Blood. 74. 1295-1302 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Muroi,K.,Ito,M.,Sasaki,R.,Suda,T.,Sakamoto,S.,Miura,Y.: "Treatment of drug-induced agranulocytosis with granulocyte-colony stimulating factor." The Lancet. 2. 55 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suda,T.,Okada,S.,Suda,J.,Miura,Y.et al.: "A stimulatory effect of recombinant murine interleukin-7(IL-7)on B-cell colony formation and inhibitory effect of IL-1alpha." Blood. 74. 1936-1941 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Muroi,K.,Sasaki,R.,Miura,Y.,Ohyashiki,K.: "Medium pH determines the differentiation of human promyelocytic leukemia cells to basophils or eosinophils by culturing in a protein-and serum-free medium." Leukemia Research. 13. 157-163 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Akai,K.,Veda,M.,Kawanishi,G.,Miura,Y.,Suda,T.: "Experimental Hematology Today 1988" Springer Verlag, 8 (1989)

    • Related Report
      1989 Annual Research Report

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

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