Optimizing chimerism level through bone marrow transplantation and irradiation to induce long-term tolerance to composite tissue allotransplantation

Jeng Yee Lin, Feng Chou Tsai, Christopher Glenn Wallace, Wei Chao Huang, Fu Chan Wei, Shuen Kuei Liao

研究成果: 雜誌貢獻文章同行評審

16 引文 斯高帕斯(Scopus)

摘要

Background: Mixed chimerism with long-term composite tissue allotransplant (CTA) acceptance can be achieved through allogeneic bone marrow transplantation (BMT). The present study investigated the optimal chimerism level by giving different irradiation dosages to recipients to induce tolerance to CTA. Methods: Chimera were prepared using Brown-Norway and Lewis rats with strong major histocompatibility complex incompatibility. The Lewis rats received 5 mg antilymphocyte globulin (day -1 and 10) and 16 mg/kg cyclosporine (day 0-10) and were separated into groups 1, 2, 3, 4, and 5 according to the day -1 irradiation dosage: 0, 200, 400, 600, and 950 cGy, respectively. The Lewis rats were then reconstituted with 100 × 106 T-cell-depleted Brown-Norway bone marrow cells (day 0) and received vascularized Brown-Norway-CTA on day 28. Chimerism was assessed monthly by flow cytometry starting on day 28 after BMT. Graft-versus-host disease (GVHD) was assessed clinically and histologically. Results: Chimerism, 4 weeks after BMT, averaged 0.2%, 9.2%, 30.7%, 58%, and 99.3% in groups 1 to 5, respectively. GVHD occurred as follows: groups 1 and 2, none; group 3, 1 case of GVHD; group 4, 7 cases of GVHD (of which 3 died); and group 5, 10 cases of GVHD (of which 6 died). The percentage of long-term CTA acceptance was 0%, 0%, 90%, 70%, and 40% in groups 1 to 5, respectively. The percentage of regulatory T cells was significantly lower in high-chimerism (≥20%, n = 15) than in low-chimerism (
原文英語
頁(從 - 到)487-493
頁數7
期刊Journal of Surgical Research
178
發行號1
DOIs
出版狀態已發佈 - 十一月 2012

ASJC Scopus subject areas

  • 手術

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