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| A bioartificial transgenic porcine whole liver expressing human proteins alleviates acute liver failure in pigs |
| Wei-Song Xue a , b , Hao-Jie Zhang a , Jing-Jing Ke c , Yu Fu a , Qing Peng a , Li Li a , Yi Gao a , d , Ke-Bo Zhong a , ∗ |
a General Surgery Center, Department of Hepatobiliary Surgery II, 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
b 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
c People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou 350000, China
d State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510280, China
∗Corresponding author.
E-mail address: zhongkb@smu.edu.cn (K.-B. Zhong). |
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Abstract 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 (hALB) and coagulation factor VII (hFVII) within a bioartificial system.
Methods: Tibetan miniature pigs were randomly subjected to different interventions after surgery-induced 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 hALB and hFVII 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). hALB and hFVII 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 hALB and hFVII ex vivo in a whole organ-based bioartificial system, while maintaining their metabolism, detoxification, transfor- mation, 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.
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2023, Vol. 22 
