title: No transmission of porcine endogenous retrovirus in an acute liver failure model treated by a novel hybrid bioartificial liver containing porcine hepatocytes.
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.
  
  
  CONCLUSIONS
  No transmission of PERVs into ALF canines suggested a reliable microbiological safety of HBAL based on porcine hepatocytes.
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China. yitaoding@hotmail.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Shi
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhong-Ze
authors.initials: ZZ
authors.lastname: Gu
authors.forename: Xian-Wen
authors.initials: XW
authors.lastname: Yuan
authors.forename: Hao-Zhen
authors.initials: HZ
authors.lastname: Ren
authors.forename: Yong
authors.initials: Y
authors.lastname: Qiu
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Ding
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D020077:Endogenous Retroviruses / Q000302:isolation & purification*; D057809:HEK293 Cells / Q000821:virology; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D017114:Liver Failure, Acute / Q000097:blood / Q000378:metabolism / Q000628:therapy*; D019164:Liver, Artificial / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis*; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D012191:Retroviridae Proteins / Q000378:metabolism*; D013552:Swine; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014777:Virus Diseases / Q000635:transmission
chemical_list: D036022:Capsid Proteins; D012367:RNA, Viral; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; D012194:RNA-Directed DNA Polymerase