A bioartificial transgenic porcine whole liver expressing human proteins alleviates acute liver failure in pigs  

作　　者：Wei-Song Xue Hao-Jie Zhang Jing-Jing Ke Yu Fu Qing Peng Li Li Yi Gao Ke-Bo Zhong 

机构地区：[1]General Surgery Center,Department of Hepatobiliary SurgeryⅡ,Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering,Guangzhou Clinical Research and Transformation Center for Artificial Liver,Institute of Regenerative Medicine,Zhujiang Hospital,Southern Medical University,Guangzhou 510280,China [2]Department of General Surgery&Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor,Nanfang Hospital,The First School of Clinical Medicine,Southern Medical University,Guangzhou 510515,China [3]People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350000,China [4]State Key Laboratory of Organ Failure Research,Southern Medical University,Guangzhou 510280,China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2023年第3期270-281,共12页国际肝胆胰疾病杂志（英文版）

基　　金：supported by grants from the National Key R&D Program of China(2018YFC1106400 and 2018YFA0108200);the National Natural Science Foundation of China(31972926);the Natural Science Foundation of Guangdong Province(2014A030312013 and 2018A030313128);Guangdong Key Research and Development Plan(2019B020234003);Science and Technology Program of Guangzhou(201803010086);Guangdong Basic and Applied Basic Research Foundation(2020A1515111111)。

摘　　要：Background:Preventing heterologous protein influx in patients is important when using xenogeneic bioartificial livers(BALs)to treat liver failure.The development of transgenic porcine livers synthesizing human proteins is a promising approach in this regard.Here,we evaluated the safety and efficacy of a transgenic porcine liver synthesizing human albumin(h ALB)and coagulation factor VII(h FVII)within a bioartificial system.Methods:Tibetan miniature pigs were randomly subjected to different interventions after surgeryinduced partially ischemic liver failure.Group A(n=4)was subjected to basic treatment;group B(n=4)was to standard medical treatment and wild-type porcine BAL perfusion,and group C(n=2)was to standard medical treatment and transgenic BAL perfusion.Biochemical parameters,coagulation status,survival time,and pathological changes were determined.Expressions of h ALB and h FVII were detected using immunohistochemistry and enzyme-linked immunosorbent assays.Results:The survival time in group A was 9.75±1.26 days;this was shorter than that in both perfused groups,in which all animals reached an endpoint of 12 days(P=0.006).Ammonia,bilirubin,and lactate levels were significantly decreased,whereas albumin and fibrinogen levels were increased after perfusion(all P<0.05).h ALB and h FVII were detected in transgenic BAL-perfused pig serum and ex vivo in the liver tissues.Conclusions:The humanized transgenic pig livers could synthesize and secrete h ALB and h FVII ex vivo in a whole organ-based bioartificial system,while maintaining their metabolism,detoxification,transformation,and excretion functions,which were comparable to those observed in wild-type porcine livers.Therefore,the use of transgenic bioartificial whole livers is expected to become a new approach in treating acute liver failure.

关 键 词：Acute liver failure Transgenic pig Bioartificial liver XENOTRANSPLANTATION 

分 类 号：R575.3[医药卫生—消化系统]