陈蕾佳, 崔梦一, 宋翔宇, 等. 人源化基因修饰猪红细胞与人血清免疫相容性的体外研究[J]. 器官移植, 2024, 15(3): 415-421. DOI: 10.3969/j.issn.1674-7445.2023226
引用本文: 陈蕾佳, 崔梦一, 宋翔宇, 等. 人源化基因修饰猪红细胞与人血清免疫相容性的体外研究[J]. 器官移植, 2024, 15(3): 415-421. DOI: 10.3969/j.issn.1674-7445.2023226
Chen Leijia, Cui Mengyi, Song Xiangyu, et al. In vitro study of immunocompatibility of humanized genetically modified pig erythrocytes with human serum[J]. ORGAN TRANSPLANTATION, 2024, 15(3): 415-421. DOI: 10.3969/j.issn.1674-7445.2023226
Citation: Chen Leijia, Cui Mengyi, Song Xiangyu, et al. In vitro study of immunocompatibility of humanized genetically modified pig erythrocytes with human serum[J]. ORGAN TRANSPLANTATION, 2024, 15(3): 415-421. DOI: 10.3969/j.issn.1674-7445.2023226

人源化基因修饰猪红细胞与人血清免疫相容性的体外研究

In vitro study of immunocompatibility of humanized genetically modified pig erythrocytes with human serum

  • 摘要:
      目的   探讨野生型(WT)、四基因修饰(TKO/hCD55)和六基因修饰(TKO/hCD55/hCD46/hTBM)猪红细胞与人血清的免疫相容性和免疫差异。
      方法  收集20名不同血型志愿者的血液,将WT、TKO/hCD55和TKO/hCD55/hCD46/hTBM猪红细胞、ABO-相容(ABO-C)及ABO-不相容(ABO-I)人红细胞分别暴露于不同血型人血清中,检测血凝集、抗原抗体结合(IgG、IgM)水平和补体依赖细胞毒性,评估2种基因修饰猪红细胞与人血清的免疫相容性。
      结果  ABO-C组未出现明显凝集;WT组和ABO-I组凝集水平高于TKO/hCD55组和TKO/hCD55/hCD46/hTBM组(均为P<0.001)。WT组猪红细胞裂解水平高于ABO-C组、TKO/hCD55组和TKO/hCD55/hCD46/hTBM组;ABO-I组猪红细胞裂解水平高于TKO/hCD55组、TKO/hCD55/hCD46/hTBM组(均为P<0.01)。TKO/hCD55组猪红细胞IgM和IgG结合水平均低于WT组和ABO-I组;TKO/hCD55/hCD46/hTBM组猪红细胞IgG和IgM结合水平低于WT组,IgG低于ABO-I组(均为P<0.05)。
      结论  基因修饰猪红细胞的免疫相容性优于野生型猪,并接近于ABO-C,人源化猪红细胞在血资源奇缺时可考虑作为血液来源。

     

    Abstract:
      Objective   To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum.
      Methods  The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated.
      Results  No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05).
      Conclusions  The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.

     

/

返回文章
返回