<i>In vitro</i> study of immunocompatibility of humanized genetically modified pig erythrocytes with human serum

Leijia Chen; Mengyi Cui; Xiangyu Song; Kai Wang; Zhibo Jia; Liupu Yang; Yanghui Dong; Haochen Zuo; Jiaxiang DU; Dengke Pan; Wenjing XU; Hongbo Ren; Yaqun Zhao; Jiang Peng

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

VernacularTitle: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
Author: Leijia CHEN ^{1
,

2
,

3} ; Mengyi CUI ³ ; Xiangyu SONG ^{1
,

2
,

3} ; Kai WANG ³ ; Zhibo JIA ^{1
,

3} ; Liupu YANG ^{1
,

3} ; Yanghui DONG ^{1
,

3} ; Haochen ZUO ³ ; Jiaxiang DU ³ ; Dengke PAN ³ ; Wenjing XU ³ ; Hongbo REN ³ ; Yaqun ZHAO ³ ; Jiang PENG ³
Author Information

1. Graduate School of Hebei North University , Zhangjiakou 075132, China
2.
3. .
Publication Type:OriginalArticle
Keywords: Blood transfusion; Xenotransplantation; Genetically modified pig; Heterologous antigen; Red blood cell; Antigen-antibody binding; Agglutination; Complement-dependent cytotoxicity
From: Organ Transplantation 2024;15(3):415-421
CountryChina
Language:Chinese
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.