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Treatment of arthritic model mice using hematopoietic stem cells simultaneously transfected with genes for anti-inflammatory cytokines and chemokine receptors

Research Project

Project/Area Number 13670470
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionJichi Medical School

Principal Investigator

MINOTA Seiji  Jichi Medical School, Dept of Medicine, Professor, 医学部, 教授 (30211593)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Keywordsgene therapy / gene transfer / hematopoietic stem cell / rheumatoid arthritis / chemokine receptor / retrovirus / リンパ球 / 遺伝子治療 / 慢性関節リウマチ
Research Abstract

The purpose of this study is to utilize hematopoietic stem cells as a vehicle of the anti-inflammatory cytokines in the arthritic model mice. T cells derived from these hematopoietic stem cells must go preferentially to the inflammed joints in order to take better effect. Two putative genes were chosen : chemokine receptor (CCR4) and IL-10. The former is to direct T cells to the inflammed joints and the latter is for anti-inflammatory effect. These genes need to be transfected simultaneously in a single hematopoietic stem cell.
As a preliminary experiment, peripheral T cells were used instead of hematopoietic stem cells from bone marrow, because transfection efficacy is much better for peripheral T cells than for hematopoietic stem cells. Gene for green fluorescent protein (GFP) was incorporated into retrovirus and was transfected to peripheral T cells as a reporter gene along with chemokine receptor or IL-10. Transfection efficacy was increased to "30% from 10% by repeating transfection processes on the fibronectin-coated plate including anti-CD3 and anti-CD28 antibodies.
Arthritic model mice were made by subcutaneous injections into DBA/1 mice of bovine type II collagen emulsified with Freund's complete adjuvant, booted with the same antigen in incomplete adjuvant 3 weeks afer the first immunization. By the biginning of the fourth week, many joints from immunized mice began to swell and arthritis became evident. However, the severity and the frequency of the artificial arthritis made by this method were quite diverse and, therefore, evaluation of the effectiveness of the treatment is quite difficult. Experimentation to overcome this issue is now undergoing.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

Research Products

(27 results)

All Other

All Publications (27 results)

  • [Publications] Hirata, D., Nagashima, T., Okazaki, H., Minota, S.: "Elevated mucle enzymes in a patient with severe hypocalcemia mimicking polymyositis"Modern Rheumatol. 12. 186-189 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwamoto, M., Nara, H., Minota, S., Nishimoto, N.: "Humanized monoclonal anti-interleukin-6 receptor antibody for treatment of intractable adult-onset Still's disease"Arthritis Rheum. 46. 338-3389 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuyama, J., Kaga, S., Kano, S., Minota, S.: "A novel costimulation pathway via the 4C8antigen for the induction of CD4+ regulatory T cells"J Immunol. 169. 3710-3716 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okazaki, H., Kakurai, M., Hirata, D., Kano, S., Minota, S.: "Characterization of chemokines receptor expression and production in circulating CD4+ T cells from patients with atopic dermatitis : up-regulation of C-C chemokine receptor 4 in atopic dermatitis"Clin Exp Allergy. 32. 1236-1242 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirata, H., Nara, H., Okazaki, H., Minota, S.: "von Recklinghausen disease in a patient with X-linked agammaglo bulinemia"Intern Med. 41. 1039-1043 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okazaki, H., Hirata, D., Kano, S., Minota, S.: "Effects of FTY72O in MRL-lpr/lpr mice : therapeutic potential in systemic lupus erythematosus"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okazaki,H., Hirata,D., Kamimura,T., Sato,H., Iwamoto,M., Yoshio,T., Masuyama,J., Fujimoto, Minota,S.: "Effects of FTY720 in MRL-lpr/lpr Mice : Therapeutic Potential in Systemic Lupus Erythematosus"J Rheumatol. 29. 707-716 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirata,D., Nara,H., Inaba,T., Muroi,R., Kanegame,H., Minota,S.: "von Reckinghausen Disease in a Patient with X-linked Agammaglobulinemia"Internal Medicine. 41. 1039-1043 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kaneko,N., Masuyama,J., Nara,H., Hirata,D., Iwamoto,H., Okazaki,H., Minota,S.and Yoshio,T.: "Production of thromboxane A2 and prostaglandin 12 affected by interaction of heat aggregated IgG, endothelial cells, and platelets in lupus nephritis"J Rheumatology. 29. 2106-2113 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuyama,J., Kaga,S., Kano,S.and Minota,S.: "A novel costimulation pathway via the 4C8 antigen for the induction of CD4+ regulatory T cells"J Immunol. 169. 3710-3716 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwamoto,M., Nara,H., Hirata,D., Minota,S., Nishimoto,N.and Yoshizaki,K.: "Humanized monoclonal anti-interleukin-6 receptor antibody for treatment of intractable adult-onset Still's disease"Arth & Rheum.. 46(12). 3388-3389 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okazaki,H., Kakurai,M., Hirata,D., Sato,H., Kamimura,T, Onai,N., Matsushima,K., Nakagawa,H., Kano,S.and Minota,S.: "Characterization of chemokine receptor expression and cytokine production in circulating CD4+ T cells from patients with atopic dermatitis : up-regulation of C-C chemokine receptor 4 in atopic dermatitis"Clin Exp Allergy. 32. 1236-1242 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikeda,M., Okazaki,H.and Minota,S.: "Cogan's syndrome with antineutrophil cytoplasmic autoantibody"Ann Rheum Dis. 61. 761-762 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirata,D., Nagashima,T., Saito,S., Okazaki,H., Kano,S.and Minota,S.: "Elevated muscle enzymes in a patient with severe hypocalcemia mimicking polymyositis"Mod Rheumatol. 12. 186-189 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagashima,T., Hirata,D., Yamamoto,H., Okazaki,H.and Minota,S.: "Antineutrophil cytoplasmic autoantibody specific for proteinase 3 in a patient with shunt nephritis induced by gemella morbillorum"Am.J.Kidney Dis.. 37. E38 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirata, D., Nagashima, T., Okazaki, H., Minota, S.: "Elevated muscle enzymes in a patient with severe hypocalcemia mimicking polymyositis"Mod Rheumatol. 12. 186-189 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwamoto, M., Nara, H., Minota, S., Nishimoto, N.: "Humanized monoclonal anti-interleukin-6 receptor antibody for treatment of intractable adult-onset Still's disease"Arth & Rheum. 46. 3388-3389 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masuyama, J., Kaga, S., Kano, S., Minota, S.: "A novel costimulation pathway via the 4C8 antigen for the induction of CD4+ regulatory T Cell"J Immunol. 169. 3710-3716 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okazaki, H., Kakurai, M., Hirata, D., Kano, S., Minota, S.: "Characterization of chemokine receptor expression and cytokine production in circulating CD4+ T cells from patients with atopic dermatitis : up-regulation of C-C chemokine receptor 4 in atopic dermatitis"Clin Exp Allergy. 32. 1236-1242 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirata, D., Nara, H., Okazaki, H., Minota, S.: "von Reckinghausen Disease in a Patient with X-linked Agammaglobulinemia"Internal Medicine. 41. 1039-1043 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okazaki, H., Hirata, D., Kano, S., Minota, S.: "Effects of FTY720 in MRL-1pr/1pr Mice : Therapeutic Potential in Systemic Lupus Erythematosus"J Rheumatol. 29. 707-716 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagashima, T., Hirata, D., Yamamoto, H., Okazaki, H., Minota, S: "Antineutrophil cytoplasmic autoantibody specific for proteinase 3 in a patient with shunt nephritis induced by gemella morbillorum"Am. J. Kidney Dis.. 37. E38 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuraiwa, K., Arai, Y., Okazaki, H., Minota, S., Tominaga, S: "Identification of human ST2 protein in the sera of patients with autoimmune diseases"Biochem Biophys Res Commun.. 284. 1104-1108 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikeda, U., Shimpo, M., Ikeda, M., Minota, S., Shimada, K: "Lipophilic stains augment inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes"J. Cardiovasc Pharmacol.. 38. 69-77 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hojo, Y., Ikeda, U., Ohya, K., Ichida, M., Kario, K., Takahashi, M., Ikeda, M., Minota, S: "Interaction between monocytes and vascular endothelial cells induces adrenomedullin production"Atherosclerosis. 155. 381-387 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Horie, S., Minota, S., Kano, S: "Large macrophage colony-forming cells in peripheral blood of patients with collagen vascular diseases : high occurrence among patients with systemic sclerosis and dermatonyositis"J. Rheumatol. 27. 2378-2381 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mimori, A., Suzuki, T., Nakajima, K., Masuyama, J., Yoshio, T., Kano, S., Minota, S: "Clinical features of dermatomyositis in the presence or absence of malignancy"APLAR J. Rheumatol.. 3(3). 217-220 (2000)

    • Related Report
      2001 Annual Research Report

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Published: 2002-03-31   Modified: 2016-04-21  

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