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No transmission of porcine endogenous retrovirus in an acute liver failure model treated by a novel hybrid bioartificial liver containing porcine hepatocytes |
Bing Han, Xiao-Lei Shi, Yue Zhang, Zhong-Ze Gu, Xian-Wen Yuan, Hao-Zhen Ren, Yong Qiu and Yi-Tao Ding |
Nanjing, China
Author Affiliations: Department of Hepatobiliary Surgery (Han B, Shi XL, Yuan XW, Ren HZ and Ding YT) and Department of Osteology (Qiu Y), the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China; Department of General Surgery, the Third Affiliated Hospital of Suzhou University, Changzhou 213000, China (Zhang Y); and State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210008, China (Gu ZZ)
Corresponding Author: Yi-Tao Ding, Professor, Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing 210008, China (Tel: +86-25-83304616ext66866; Fax: +86-25-83317016; Email: yitaoding@hotmail.com) |
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Abstract BACKGROUND: A novel hybrid bioartificial liver (HBAL) was constructed using an anionic resin adsorption column and a multi-layer flat-plate bioreactor containing porcine hepatocytes co-cultured with bone marrow mesenchymal stem cells (MSCs). This study aimed to evaluate the microbiological safety of the HBAL by detecting the transmission of porcine endogenous retroviruses (PERVs) into canines with acute liver failure (ALF) undergoing HBAL.
METHODS: Eight dogs with ALF received a 6-hour HBAL treatment on the first day after the modeling by D-galactosamine administration. The plasma in the HBAL and the whole blood in the dogs were collected for PERV detection at regular intervals until one year later when the dogs were sacrificed to retrieve the tissues of several organs for immunohistochemistry and Western blotting for the investigation of PERV capsid protein gag p30 in the tissue. Furthermore, HEK293 cells were incubated to determine the in vitro infectivity.
RESULTS: PERV RNA and reverse transcriptase activity were observed in the plasma of circuit 3, suggesting that PERV particles released in circuit 3. No positive PERV RNA and reverse transcriptase activity were detected in other plasma. No HEK293 cells were infected by the plasma in vitro. In addition, all PERV-related analyses in peripheral blood mononuclear cells and tissues were negative.
CONCLUSION: No transmission of PERVs into ALF canines suggested a reliable microbiological safety of HBAL based on porcine hepatocytes.
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