| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Research Abstract |
Hand transplantations have revolutionized the reconstruction field for patients with hand defects. However, immunosuppressants are essential for maintaining human hand transplant survival despite lethal side effects such as infections, drug toxicity and malignancies. Recent studies indicate that mesenchymal stem cells(MSCs) have some immunomodulatory properties to suppress T cell mediate responses that cause graft rejection. The purpose of this study is to evaluate the effect of intravenous donor MSC infusion for immunomodulation in the rat composite tissue allotransplantation model.
Orthotopic rat hind limb transplantation was performed using donor Wister rats and recipient Lewis rats. The recipient rats were randomly divided into two experimental groups : in group FK, 0.2 mg/kg/day intramuscular tacrolimus were administered to recipient rats for seven consecutive days(days 0.6); in group MSC, recipient rats were injected intravenously with 2×10^6 donor MSCs on day 6 with 0.2 mg/kg/day tacrolimus administered for 7 days.
Graft survival was assessed by daily inspection and histological study. Recipients' immunological reactions were evaluated by serum ELISA, RNA assays and mixed lymhocyte reactivity assays.
The graft survival of group MSC was significantly prolonged in comparison with that of group FK. Cytokine expression analysis of grafted limbs showed that MSC treatment significantly decreased pro-inflammatory cytokine expression. An in vitro mixed lymphocyte reaction showed MSCs inhibiting T cell proliferation.
MSCs induce T cell hyporesponsiveness and prolong graft survival in the rat composite allotransplantation model. MSCs demonstrate some immuno-modulatory properties that can be accomplished without the need for significant recipient immunosuppression.
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