人／猪造血嵌合体构建及特异性免疫耐受形成的初步研究  

Construction of human -to -swine hematopoiedc chimera model and study on its specific immune tolerance

作　　者：赵树铭[1] 刘真[1] 蒋天伦[1] 范娅涵[1] 王昕[1] 

机构地区：[1]第三军医大学西南医院输血科,重庆400038

出　　处：《中国输血杂志》2008年第1期17-21,共5页Chinese Journal of Blood Transfusion

基　　金：重庆市自然科学基金(CSTC.2004BB5074);第三军医大学科研创新基金资助项目(2007XG51)

摘　　要：目的初步探析人/猪造血嵌合体的构建及所诱导形成特异性免疫耐受的条件,为实现嵌合体人源性造血提供实验支持。方法实验分为3组,新生猪5只/组,实验1组:将人脐血来源CD34+细胞移植入正常新生小型猪体内后,持续注射人源SCF、EPO;实验2组:新生猪移植细胞后不注射人源因子;实验3组(正常对照组):新生猪注射生理盐水。移植后10、20、30、40、50、60d时取嵌合体猪外周血,检测人源CD71+细胞比例,同时检测猪外周血抗人种属抗体。结果2组嵌合体猪外周血中均有一定比例的人源CD71+细胞,但实验1组外周血比例显著高于同期实验2组(P<0.01);正常小型猪外周血于16d出现抗人种属抗体,嵌合体猪外周血于移植后50d出现,且抗体效价低于同龄正常猪。结论利用新生乳猪可建立人/猪造血嵌合体,可诱导形成供者型免疫耐受;在人源造血因子作用下,可实现人造血干细胞在嵌合体内分化。Objective To explore the conditions for construction of human-to-swine hematopoietic chimera and its specific immune tolerance.Methods The human cord blood CD34^＋ cells （5×10^5/Kg） were transplanted to neonatal swine through intraperitoneal injections. The experimental swine, injected with human SCF （50ng/Kg.3d） and EPO （100U/Kg. 3d） simultaneously, and swine without injection were defined as transplantation group 1 and group 2, respectively. The swine, injected with saline, were taken as the control group. Peripheral blood （PB） was collected on day 10, 20, 30, 40, 50, and 60 after injection. The human CD71 ＋cells in the chimera PB were quantitated by FACS and the genus-antibodies of PB were detected by blood group gel card. Results The percentage of human CD71 ＊ cells in PB of transplantation group 1 was significantly higher than that of group 2 （P〈0.01）. The genus-antibodies against human cells could be detected on day 16 in the control group, and on day 50 in the chimera groups 1 and 2. The antibody titers in the chimera groups were lower than those of the same age control swine. Conclusion The human-to-swine hematopoietic chimera and its specific immune tolerance were constructed successfully in neonatal swine. Human HSC in chimera could differentiate into human blood cells with stimulation by human hematopoietic cytokines.

关 键 词：猪 人 异种移植 脐血 造血干细胞 嵌合体 

分 类 号：R446[医药卫生—诊断学]