外周血单个核细胞
医学
丝裂霉素C
同种异体移植
外周血
外围设备
外科
免疫学
移植
化学
内科学
体外
生物化学
作者
Christian Andreas Radu,Jurij Kiefer,Dominik Horn,Christian Kleist,Laura Dittmar,Flavius Sandra,Martin Rebel,H. Ryssel,Eva Koellensperger,Martha Maria Gebhard,Marcus Lehnhardt,Guenter Germann,Peter Terness
标识
DOI:10.1016/j.jss.2011.12.032
摘要
Background Composite tissue allotransplantation (CTA) was introduced as a potential treatment for complex reconstructive procedures and has become a clinical reality. Hand and face transplantation, the most widely recognized forms of CTA, have intensified immunological research in this emerging field of transplantation. Mitomycin C (MMC) is an alkylating agent that suppresses allogeneic T-cell responses. MMC-treated dendritic cells/PBMCs have been shown to induce donor-specific tolerance in solid organ allograft transplantations. Methods Fully mismatched rats were used as hind limb donors [Lewis (RT11)] and recipients [Brown-Norway (RT1n)]. Fifty-five allogeneic hind limb transplantations were accomplished in six groups. Group A (n = 10) received donor-derived MMC-treated PBMCs on transplantation day. Group B (n = 10) rats received no immunosuppression, group C (n = 10) received FK506 and prednisolon, group D consisted in isograft transplantation without immunosuppression, group E (n = 10) received non-treated PBMCs, and group F (n = 5) received PBS without any donor-derived cells. Rejection was assessed clinically and histologically. Results In group A, the survival times of the allografts were prolonged to an average of 8.0 d. Rejection was significantly delayed compared with the averages of the corresponding control groups B, E, and F (5.5, 5.9, and 5.8 d). No rejection was seen in control groups C and D. Conclusion These results demonstrate that MMC-treated donor PBMCs significantly prolong allograft survival when administered systemically on the day of transplantation. However, the immunomodulatory effect is relatively modest with further research being required to clarify dose–effect relations, cell characteristics, and an optimized mechanism and timing for cell application.
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