供体外周血干细胞在活体肾脏移植中的应用研究  

Clinical study of infusion of peripheral blood stem cells of the donor to renal transplantation recipient

作　　者：石炳毅[1] 蔡明[1] 陈忠华 钱叶勇[1] 艾辉胜[3] 詹胜利[1] 周文强[1] 王亚炜[1] 

机构地区：[1]解放军总医院第二附属医院器官移植中心,北京100091 [2]华中科技大学同济医学院器官移植研究所 [3]解放军第307医院血液科

出　　处：《解放军医学杂志》2006年第10期1011-1013,共3页Medical Journal of Chinese People's Liberation Army

基　　金：全军"十五"计划重大项目(01Z097);国家重点基础研究发展计划资助项目(2003CB515505)

摘　　要：目的研究活体肾移植受体接受全身淋巴结照射(TLI)预处理基础上输注供体外周血干细胞(PBSCs)后嵌合体形成情况及其与肾移植的相关性。方法5对供受体进入本研究。供体平均年龄40岁,受体平均年龄27岁。HLA-A、B、DR6个抗原中4个抗原错配1例,3个抗原错配2例,1个抗原错配2例。TLI治疗从移植手术前5天开始,90cGy/d,共5天。术中和术后的免疫抑制药物方案与同时期的活体或尸体肾移植相同,但剂量略减少。供体的PBSCs动员使用瑞雪新,150μg/d,共5天,PBSCs采集和输注共2次,分别在移植手术后的第4、7天。术后应用PCR-SSP检测外周血嵌合体阳性率和持续时间。观察免疫抑制药物的使用情况、移植肾状态和急性排斥反应频率及GVHD等。结果供体经5天的G-CSF动员后,采集的PBSCs平均数为34×106。移植术后1个月5例受体外周血中均可检测到供体的HLD-DR抗原成分。2个月后4个HLA抗原错配,其中HLA-DR均错配的受体外周血中嵌合体PCR检测阴性,3个月后HLA-DR均错配和1个HLA-B错配的受体外周血嵌合体检测阴性,受体3、4和5的外周血中供体DNA仍为阳性。PBSCs输注后没有发生GVHD,没有任何感染发生。观察期内没有发生移植肾排斥反应,移植肾功能正常。免疫抑制剂使用量低于同时期的其他活体肾脏移植和尸体肾脏移植受体。结论非清髓性的TLI治疗可以促进供体PBSCs植入受体造血系统,诱导产生造血嵌合体,而造血嵌合体的形成可以减少肾脏移植的排斥反应,减少免疫抑制剂的应用,提高移植物的长期存活率。PBSCs的采集和输注简便、有效,痛苦小,是一种理想的造血干细胞输注源。Objective To study the chimerism formation in kidney transplantation recipient receiving peripheral blood stem cells （PBSCs） of the donor after the patient received preoperative total lymphoid irradiation （TLI）. Methods 5 patients of living donor kidney transplantation were involved in present study. The mean age of donors was 40 and that of recipients was 27. There was one patients with 4 HLA antigen mismatches out of 6 HLA-A, B, DR antigens, two patients with 3 HLA-mismatches, and two patients with 1 HLA-mismatch. The patients received TLI in doses 90cGy/d from day -5 to day -1. The immunosuppression protocol for these patients during operation and afteroperation was similar to that for other cases, but the dosage was slightly reduced. Donor PBSCs were harvested twice via leukapheresis after the administration of human reeombinant granulocyte colony stimulating factor （G-CSF）. PBSCs were infused intravenously to the recipients on postoperative day 4 and 7. Chimerism of peripheral blood cell in recipients was detected by PCR-SSP assays. The grafted kidney function, acute rejection frequency and GVHD episodes were also observed. Results After 5 days of G-CSF based mobilizing regimen, the average number of PBSCs harvested from donors was 34 × 10^6. At 1 month post-transplantation, donor type HLADR gene was detected in all the recipients. At 2 and 3 months post-transplantation, chimerism was not detectable in the recipient with 4 HLA antigens （including 2 HLA DR） mismatched donor kidney and in the recipient with 3 HLA （including 2 HLA-DR and 1 HLA-B） mismatched donor, respectively. In the other 3 recipients, chimerism was still positive 3 months post-transplantation. There were no symptoms of GVHD or infections after infusion of PBSCs. Transplanted kidneys functioned normally and rio rejection episodes were observed till the end of the study. The immunosuppressant dosage was lower for these 5 cases than those after conventional cadavar renal transplantation. Conclusions Non-myeloablative TLI co

关 键 词：供体外周血干细胞 活体肾脏移植 应用 研究 

分 类 号：R699.2[医药卫生—泌尿科学]