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Basic study towords reconstitution of normal and leukemic human hemopoiesis in small monkey of common marmoset

Research Project

Project/Area Number 11557073
Research Category

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

Allocation TypeSingle-year Grants
Section展開研究
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

TANI Kenzaburo  IInst of Med Sci Univ of Tokyo, Associate Professor, 医科学研究所, 助教授 (00183864)

Co-Investigator(Kenkyū-buntansha) HAMADA Hiromi  Tsukuba University Assistant Professor, 医学専門学群, 講師 (60261799)
TANIOKA Yoshikuni  The Central for Experimental Animals, Chief of Animal Experimentation Center, 実験動物センター, センター長(研究職) (10072406)
ASANO Shigetaka  Inst of Med Sci Univ of Tokyo, Professor, 医科学研究所, 教授 (50134614)
ISEKI Tohru  IInst of Med Sci Univ of Tokyo, Research Associate, 医科学研究所, 助手 (10232365)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1999: ¥8,100,000 (Direct Cost: ¥8,100,000)
Keywordscommon marmoset / human hematopoiesis model / leukemia model / xenograft / CD34 positive cell / cord blood cells / chimera hematopoiesis / gene transfer / 臍帯血細胞 / 胎児移植 / CD34 / フローサイトメトリー
Research Abstract

For the purpose of constructing preclinical monkey models with normal and leukemic human hematopoiesis, we have introduced small monkey of common marmoset. The followings are the progress in this year.
1) Construction of normal and leukemic human hematopoiesis in marmoset :
We transplanted CD34 positive human umbilical cord blood cells intraperitoneally to marmoset fetus under the guide of ultrasonograph. We have so far transplanted the CD34 positive human cord blood cells to 16 fetuses in 8 mother marmosets. We have also transplanted human leukemia cells of BV173, IMS-BC1 or Meg-01 to 14 fetuses in 7 mother marmosets. In the beginning abortions followed by the transplantations were experienced but the techniques have been improved using highly sensitive ultrasonography. Now we are following up carefully the in vivo constitution of human/marmoset chimera hematopoiesis in newborn marmosets.
2) Characterization of common marmoset lymphocytes : We have isolated marmoset lymphocyte fractions which were positive for human CD4, CD8 or CD56 monoclonal antibodies. The lymphocytes positive for human CD4 or CD8 antibody were considered also to be functional in marmosets. CD56 positive lymphocytes should furthermore be characterized to elucidate its characters.
We have so far demonstrated the similar characters of hematopoietic cells and lymphocytes between human and common marmosets. These findings support the possibility of constructing marmoset with human/marmoset hematopoietic chimera. Such marmosets would be very beneficial to study the safety and efficacy of newly developed gene transfer vectors as well as biological modifiers at preclinical levels. Although we have not successfully constructed such chimera marmosets yet, we have developed several new strategies which would make the xenografting more safely and efficiently. Further experiment is required to construct marmoset preclinical model system to study normal and leukemic human hematopoiesis.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Tanabe T.,Tani,K.,et at.: "Suppression of progression of chronic myelogenous leukemia in mice by an allosterically controlled ribozyme."Nature. 406. 473-474 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wu,M-S.,Tani,K.,et al.: "MHC (Major Histocompatibility Complex)-DRB Genes and Polymorphisms in Common Marmoset."J.Mol Evol. 52. 214-222 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanabe T.,Tani,K.,et al.: "Maxizyme, novel allosterically controllable ribozymes, can be designed to cleave various substrates. "Biomacromolecules. 1. 108-117 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Watari,K.,Tani,K.,et al.: "Hyperfunction of neutrophils in a BCR/ABL-negative chronic myeloid leukemia : A case report with in vitro studies."Cancer. 89. 551-560 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tani,K.,et al.: "Progress reports on immune gene therapy for stage IV renal cell cancer using lethally irradiated granulocyte-macrophage colony-stimulating factor-transduced autologous renal cancer cells"Cancer Chemother Pharmacol. 46. S73-S76 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 谷憲三朗、浅野茂隆: "遺伝子治療の新展開-遺伝子治療研究の現状と将来"羊土社. 10-18 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 谷憲三朗他: "分子細胞治療vol.1免疫遺伝子治療の新展開"先端医学社. 48-53 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hibino H., Tani K., Tanioka.Y., Asano.S., et al.: "Common Marmoset as a Target Preclinical Primate for Cytokine and Gene Therapy Studies."Blood. 93. 2839-2848 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohata, J., Tani, K., Asano S., et al.: "CD4/CD8 double-positive adult T cell leukemia with preceding cytomegaloviral gastroenterocolitis."Int J Hematol.. 69. 92-95 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tani, K., Tanioka, Y., Asano, S.et al.: "Hematological Aspects of Common Marmoset Monkey Transplanted with autologous MDR1 gene transduced peripheral blood stem cells."Molecular Biology of Hematopoiesis. 6. 307-3

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okuno S, Hamada H, et al.: "Brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP) levels in normal pregnancy and preeclampsia."J Obstet Gynaecol Res.. 25 (6). 407-10 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hamada H, et al.: "New ultrasonographic criterion for the prenatal diagnosis of cloacal exstrophy : elephant trunk-like image."J Urol.. 162 (6). 2123-4 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tani, K., Asano S., et al.: "Progress reports on immune gene therapy for stage IV renal cell carcinoma using lethally irradiated GM-CSF transduced autologous renal cancer cells."Cancer Chemotherapy & Pharmacology. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanabe T.Tani K.Asano S.et al.: "Maxizyme, novel allosterically controllable ribozymes, can be designed to cleave various substrates."Biomacromolecules. 1. 108-117 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hase, H., Tani, K., Iseki, T., Asano, S., et al.: "Case Rerort : The avalability of TCR-Vβ repertoires analysis with RT-PCR methods for the early detection of pulmonary relapsed T-cell malignancy after the autologous stem cell transplantation."Am J Hematol. 64 (2). 124-7 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Watari, K., Tani, K., Asano, S., et al.: "Hyperfunction of neutrophils in a BCR/ABL-negative chronic myeloid leukemia : A case report with in vitro studies."Cancer. 89. 551-560 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wu, M-S., Tani, K., Isaki, T., Asano S., et al.: "MHC (Major Histocompatibility Complex)-DRB Genes and Polymorphisms in Common Marmoset."J.Mol Evol. 52. 214-222 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanabe T., Tani K., Asano S., et al.: "Suppression of progression of chronic myelogenous leukemia in mice by an allosterically controlled ribozyme."Nature. 406. 473-474 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiki Y, Hamada H, et al.: "Dominant expansion of human T cells in non-obese diabetic/severe combined immunodeficiency mice implanted with human bone fragments."Exp Hematol.. 28 (7). 792-801 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamada N, Hamada H.et al.: "The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia."J Hum Genet.. 45 (3). 138-41 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hibino H., Tani K., Iseki, T., Tanioka Y., Asano, S., et al.: "Haematopoietic progenitor cells from common marmoset as targets of gene transduction by retroviral and adenoviral vectors."Eur J Haematol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanabe T.,Tani,K., et al.: "Suppression of progression of chronic myelogenous leukemia in mice by an allosterically controlled ribozyme."Nature. 406. 473-474 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wu,M-S.,Tani,K., et al.: "MHC (Major Histocompatibility Complex) -DRB Genes and Polymorphisms in Common Marmoset."J.Mol Evol. 52. 214-222 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanabe T.,Tani,K., et al.: "Maxizyme, novel allosterically controllable ribozymes, can be designed to cleave various substrates."Biomacromolecules. 1. 108-117 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Watari,K.,Tani,K., et al.: "Hyperfunction of neutrophils in a BCR/ABL-negative chronic myeloid leukemia : A case report with in vitro studies."Cancer. 89. 551-560 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tani,K., et al.: "Progress reports on immune gene therapy for stage IV renal cell cancer using lethally irradiated granulocyte-macrophage colony-stimulating factor-transduced autologous renal cancer cells"Cancer Chemother Pharmacol. 46. S73-S76 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 谷憲三朗,浅野茂隆: "遺伝子治療の新展開-遺伝子治療研究の現状と将来"羊土社. 10-18 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 谷憲三朗 他: "分子細胞治療vol.1 免疫遺伝子治療の新展開"先端医学社. 48-53 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hibino,H.,Tani,K.,et al.: "Common Marmoset as a Target Preclinical Primate for Cytokine and Gene Therapy Studies"Blood. 93. 2829-2838 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Watari,K.,Tani,K.,et al.: "Identification of a melanoma antigen,PRAME,as a BCR/ABL-inducible gene"FEBS lett. 3(in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Hase,H.,Tani,K.,et al.: "Case Report : The avalability of TCR-Vβ repertoires analysis with RT-PCR methods for the early detection of pulmonary reapsed T-cell malignancy after the autologous stem cell transplantation"Am J Hematol. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohata,J.,Tani,K.,et al.: "CD4/CD8 double-positive adult T cell leukemia With preceding cytomegaloviral gastroenterocolitis"Int J Hematol.. 69. 1-5 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsuruta,T.,Tani,K,.et al.: "Alkaline phosphatase,defensin gene expression and effect of myeloid cell growth factors in normal and leukemic cells."Leuk Lymphoma. 32. 237-247 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tani,K.,et.al.: "Molecular Biology of Hematopoiesis"Kluwer Academic/Plenum Publishers. 13 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 谷 憲三郎: "血液悪性腫瘍に対する遺伝子治療"臨床病理. 10 (1999)

    • Related Report
      1999 Annual Research Report

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

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