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CHARACTERIZATION OF PURIFIED HUMAN HEMATOPOIETIC PROGENITOR CELLS OF BONE MARROW AND THEIR RECONSTITUTING ABILITY IN GENOGENEIC TRANSPLANTATION

Research Project

Project/Area Number 09670809
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

KOBAYASHI Masao  FACULTY OF EDUCATION,CHILD HEALTH,HIROSHIMA UNIVERSITY PROFESSOR, 教育学部, 教授 (00162016)

Co-Investigator(Kenkyū-buntansha) KATOH Osamu  RESEARCH INSTITUTE FOR RADIATION BIOLOGY AND MEDICINE,ENVIRONMENT AND MUTATIONS,, 原爆放射能医学研究所, 助教授 (90214361)
FUJITA Naoto  UNIVERSITY HOSPITAL,PEDIATRICS,RESEARCH ASSOCIATE, 医学部・附属病院, 助手 (60274081)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsHematopoietic progenitors / Hematopoietic factors / Cell sorting / Xenogeneic transplantation / Severe congenital neutropenia / 造血前駆細胞
Research Abstract

We have tested the effects of early-acting hematopoietic factors on the proliferation of primitive human bone marrow progenitor cells in serum-deprived culture, and the engrafting capability of purified primitive human bone marrow cells using the NOD/SCID/human xenograft model. Primitive human bone marrow cells were purified by setting the FAGS Vantage based on the expression of CD34, Kit receptor and CD38. The results of single-cell culture system suggest that steel factor (SF), the ligand for flk2/flt3 (FL) and thrombopoietin (TPO) play important roles in survival and proliferation of primitive human hematopoietic progenitors.
The engrafting capabilities of the primitive bone marrow cells were examined by injecting them into NOD/SCID mice. As marker for engraftment, we analyzed CD45-positive cells and human specific DNA using PCR The day-90 engraftment in the bone marrow was seen with fresh cells (CD34^+/Kit^+) but not with cells cultured in the presence of SF, FL and TPO.To evaluate the engrafting capability of cultured cells, the development of culture system using the combination of hematopoietic factors might be required.
We studied the responsiveness of primitive myeloid progenitor cells to hematopoietic factors in four patients with SCN.The number of granulocyte-macrophage (GM) colonies formed in patients was decreased in response to granulocyte colony-stimulating factor (G-CSF) in both serum-supplemented and serum-deprived culture. The results suggest that primitive myeloid progenitor cells of patients with SCN have defective responsiveness to not only G-CSF but also the early- or intermediate-acting hematopoietic factors, SF, FL, and IL-3.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Masao Kobayashi et al.: "Thrombopoietin,steel factor,and ligand for tlt3/tlk2 interact to stimulate the probiteration of human heuntopoistic progenitore in culture." International Journal of Hematology. 66. 423-434 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshifumi Shimizu,et al.: "Engraftment of cultured human hematopoietic cells in cheep." Blood. 91. 3688-3692 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osamu Katoh,et al.: "VEEGF inhibits apoptotic death in hemotopoietic cells after exposure to chemotherapeutic drugs by inducing MCL1 acting as an apoptotic factor." Cancer Research. 58. 5565-5569 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shin-ichiro Miyagawa et al.: "Abnormal responsers of primitive myeloid progenitors in patients with SCN" Blood. 92. 536a (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masao Kobayashi, Joseph H.Laver, Takashi Kato, Hiroshi Miyazaki, and Makio Ogawa: "Thrombopoietin, steel factor and the ligand for flt3/flk2 interact to stimulate the proliferation of human hematopoietic progenitors in culture." International Journal of Hematology. 66(3). 423-434 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshifumi Shimizu, Makiko Ogawa, Masao Kobayashi, Grace Almeida-Porada, Esmail D Zanjani: "Engraftment of cultured human hematopoietic cells in sheep." Blood. 91(10). 3688-3692 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osamu Katoh, Toshiaki Takahashi, Tetsuya Oguri, Ken Kuramoto, Keiichiro Mihara, Masao Kobayashi, Shitau Hirata & Hiromitsu Watanabe: "Vascular endothelial growth factor inhibits apoptotic death in hematopoietic cells after exposure to chemotherapeutic drugs by inducing MCL1 acting as an anti-apoptotic factor." Cancer Research. 58. 5565-5569 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shin-chiro Miyagawa, Masao Kobayashi, Nakao Konishi, Osamu Katoh, Kazuhiro Ueda: "Abnormal responses of primitive myeloid progenitors in pateints with severe congenital neutropenia." American Society of Hematology, 40th Annual Meeting, Miami Beach, FL 1998.12.Blood. 92(10). 536a (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masao Kobayashi,et al.: "Thrombopoietin,steel tactor,and the bgand for flt3/tek2 interact to stimulate the proliteratipn at luman henatopoietic progem fors in culture" International Journal of Haematology. 66. 423-434 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshitumu Shimizu,et al.: "Engrattrent ot cultured human hematopoietic cells in sheep" Blood. 91. 3688-3692 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Osamu Katoh,et al.: "Vascular endothelsal growth factor inhibitc apoptotic death in hematopoietic cells attes oxposure to clowstheapeutic diugs by inducing MCLI" Cances Reseasch. 58. 5565-5569 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masao Kobayashi, et al: "Thrombopoietin,steelfactor,and the ligand for flt3/flk2 interact to stimulate the proliferation of human hematopoietic progenitors in culture" International Journal of Hematology. 66. 423-434 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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