Consistent Liver Function Support from Gene-Edited Pigs to Non-Human Primate Acute Liver Failure Models via Extracorporeal Liver Cross-Circulation
Year: 2026
Type: preprint
Abstract: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are severe, rapidly progressing conditions. Existing non-biological artificial liver support has limited efficacy, and liver transplantation is constrained by donor shortage and the time window. Extracorporeal liver cross-circulation (ELC) using gene-edited (GE) pigs offers a promising bridging therapy. Here, six Tibetan macaque ALF models were connected via ELC to 8GE pig livers under normothermic machine perfusion for 74–144 h to assess feasibility and functional support. Basic vital signs of the recipients, including heart rate, body temperature, and mean arterial pressure, remained relatively stable. Their AST/ALT rose then declined, total bilirubin trended upward, albumin and total protein remained stable, and bile secretion was continuous, indicating effective replacement of impaired liver function. INR and fibrinogen remained relatively stable, while platelets dropped sharply and stayed low, suggesting generally maintainable coagulation but thrombocytopenia. Complement, immunoglobulins, and B/T/NK cells remained low, indicating good immunosuppression. Donor liver injury was mainly ischemia/reperfusion- and inflammation-mediated, without typical hyperacute or acute rejection. In summary, 8GE pig livers under room-temperature ex vivo cross-perfusion maintained stable vital signs in ALF recipients, supported liver function for >72 h in all six recipients (up to 144 h), and effectively avoided hyperacute and acute rejection, providing a feasible strategy and key data for the safety and efficacy of clinical ELC.
Source: Research Square
Authors: Hong-Jiang Wei, Yinrui Ma, Jun Ma, Chang Yang, Yinjia Wang, Kaixiang Xu, Ruichao Wu, Wenjie Zhang, Taiyun Wei, Hongfang Zhao, Zongru Li, Xiuyi Lu, Xiong Zhang, Yiran Li, Yubo Qing, Gang Su, Xudong Shen, Shuai Li, Qingyou Xu, Ronghua Xu, Xuexiang Qin, Limin Yin, Yun Dong, Shengwei Wang, Yueshen Zhu, Linfeng Zhang, Haoren Zhang, Fan Huang, Yao Fu, Jian Guo, Jipeng Shi, Xiangqian Chen, Hong-Ye Zhao, Yuan Shi, Beicheng Sun, Jianghua Ran
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225089890