African Journal of Pig Farming

ISSN 2375-0731

African Journal of Pig Farming ISSN 2375-0731 Vol. 7 (2), pp. 001-011, February, 2019. © International Scholars Journals

Full Length Research Paper

Evaluation of a reversibly immortalized human hepatocyte line in bioartificial liver in pigs

Lifu Zhao1, Jianzhou Li1, Guoliang Lv1, Anye Zhang 1, Pengcheng Zhou1, Ying Yang1, Xiaoping Pan1, Xiaopeng Yu1, Yimin Zhang1, Shusen Zheng2, Yu Chen1, Yuemei Chen1, Chengbo Yu1, Weibo Du1, Tao Song3, Jiansheng Xu3, Yang Yu3 and Lanjuan Li1*

1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.

2Department of Surgery, State Key Laboratory of Combined Multi-organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.

3Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190, China.

Accepted 25 October, 2018

Abstract

An appropriate cell source is essential for the clinical application of bioartificial liver (BAL) system. This study aimed to test a reversibly immortalized human hepatocyte line (HepLi-4) in our newly validated choanoid fluidized bed bioreactor based BAL in pigs with fulminant hepatic failure (FHF). 15 FHF pigs were allocated to three groups: a BAL group receiving BAL treatment with HepLi-4 cells; a sham BAL group receiving cell-free BAL treatment; and a FHF group receiving intensive care only. Expression of liver-specific genes in HepLi-4 cells before and after BAL was analyzed, adult human hepatocytes acted as a reference. In BAL group, Fischer index was higher and serum indirect bilirubin level was lower compared with two control groups. Survival time in BAL group was longer than that in two control groups, but the difference was not statistically significant. Gene expression analysis showed that the transcript levels of liver-specific genes in HepLi-4 were retained after BAL, but significant variations were observed between HepLi-4 and human hepatocytes. HepLi-4 showed beneficial metabolic effects on FHF pigs in BAL, but is still not an appropriate cell source for BAL. More insights into interpreting the conditions for hepatocyte differentiation are needed.

Key words: Reversible immortalization, hepatocytes, bioartificial liver, fulminant hepatic failure.

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