2002 Fiscal Year Final Research Report Summary
Treatment of arthritic model mice using hematopoietic stem cells simultaneously transfected with genes for anti-inflammatory cytokines and chemokine receptors
| Project/Area Number |
13670470
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Jichi Medical School |
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Principal Investigator |
MINOTA Seiji Jichi Medical School, Dept of Medicine, Professor, 医学部, 教授 (30211593)
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| Project Period (FY) |
2001 – 2002
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| Keywords | gene therapy / gene transfer / hematopoietic stem cell / rheumatoid arthritis / chemokine receptor / retrovirus |
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| 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.
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Research Products
(15 results)
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
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