Premium
No evidence of in vitro and in vivo porcine endogenous retrovirus infection after plasmapheresis through the AMC‐bioartificial liver
Author(s) -
Di Nicuolo Giuseppe,
Kerkhove MaartenPaul,
Hoekstra Ruurdtje,
Beld Marcel G. H. M.,
Amoroso Pietro,
Battisti Sonia,
Starace Maria,
Florio Ernesto di,
Scuderi Vincenzo,
Scala Simona,
Bracco Adele,
Mancini Antonio,
Chamuleau Robert A. F. M.,
Calise Fulvio
Publication year - 2005
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2005.00226.x
Subject(s) - xenotransplantation , infectivity , bioartificial liver device , virology , clearance , medicine , miniature swine , transplantation , hek 293 cells , in vitro , virus , biology , cell culture , hepatocyte , biochemistry , genetics , urology
Background: Currently a number of bioartificial livers (BAL) based on porcine liver cells have been developed as a treatment to bridge acute liver failure patients to orthotopic liver transplantation or liver regeneration. These xenotransplantation related treatments hold the risk of infection of treated patients by porcine endogenous retrovirus (PERV) released from the porcine cells, as in vitro infection experiments and transplantations in immunocompromised mice have shown that PERV is able to infect human cells. The Academic Medical Center (AMC)‐BAL, unlike other BALs, is characterized by direct contact between porcine liver cells and human plasma, and might therefore be permissive for PERV transfer. Methods: Prior to a clinical phase I trial, human plasma perfused through the AMC‐BAL was investigated for PERV DNA and RNA. Moreover productive infectivity was analyzed by exposing the plasma to HEK‐293 cells that were subsequently tested for PERV DNA, PERV RNA and reverse transcriptase activity. Results: Although PERV DNA was detected in the perfused plasma, no productive infectivity was detected. Consequently fourteen patients were treated with the AMC‐BAL and monitored for PERV transmission. Immediately after treatment the plasma of the patients was positive for PERV DNA, most probably due to porcine liver cell lysis. The PERV DNA was cleared within 2 weeks post‐treatment and no PERV RNA was detected. No productive infectivity in human embryonic kidney (HEK)‐293 cells exposed to plasma of treated patients was detectable. Conclusion: To conclude, no release of infective PERV particles from the AMC‐BAL was observed. Therefore we consider the AMC‐BAL as safe, however careful surveillance of patients will be continued.