AN69 Hollow Fiber Membrane will Reduce but Not Abolish the Risk of Transmission of Porcine Endogenous Retroviruses

Abstract

As the risk of porcine endogenous retrovirus (PERV) infection is a major obstacle to the xenotransplantation of porcine tissue, we investigated whether an AN69 hollow fibre membrane, used for islets of Langerhans transplantation, could prevent the transfer of PERVs and thus reduce the risk of PERV infection. PK15 cells were used as a PERV source. A specific and highly sensitive RCR was used for detection of a PERV provirus DNA (gag region) and a porcine mtDNA. Human U293 cells were incubated in vitro with encapsulated PK15 cells, concentrated encapsulated PK15 supernatant, or concentrated PK15 supernatant as a control. CD1 mice were implanted in vivo with encapsulated PK15 cells or injected with PK15 supernatant. We found no infection in human cells incubated with either encapsulated PK15 supernatant or in 10 out of 11 samples after coincubation with encapsulated PK15 cells. Infection of human cells was, however, detected in 1 out of 11 samples after coincubation with encapsulated PK15 cells. The presence of PERV provirus DNA and porcine mtDNA was detected in all the investigated tissues of the mice injected with PK15 supernatant and in various tissues of the mice implanted with encapsulated PK15 cells. Four weeks after the last injection of PK15 supernatant or a fiber explantation, no mouse showed any presence of PERV provirus DNA or porcine mtDNA. Our results demonstrate that AN69 hollow fiber membrane will reduce but not abolish the risk of PERV infection. Because the real risk of PERV infection still remains unknown, it is necessary to investigate further the real protection that could be provided by hollow fibers to ensure the safety of clinical xenotransplantation.

Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand

“…In addition, the lack of PERV transmission is consistent with preliminary studies using encapsulated porcine islets from the same donor pigs where recipient monitoring was performed for up to 9-yr post-transplant [20] and explantation of viable cells was achieved after 19 months post-transplant [55]. It also is possible that the lack of evidence for PERV infection may be due to the encapsulation of the islet cells reducing the release of PERV given that the capsule pores are smaller than the virus [56,57]. However, for the NZ DPF herd, this point is likely invalid as infectivity studies using the supernatant of cultivated encapsulated cells, and the measured reverse transcriptase activity in this supernatant have always been negative [23,38,39].…”

Xenotransplantation Literature Update January–February, 2006

“…Pakhomov et al [24] studied whether an AN69 hollow fiber membrane, used for islet transplantation, could prevent transfer of porcine endogenous retrovirus (PERV) and reduce the risk of PERV infection. PK15 cells were used as a PERV source, and a specific and highly sensitive polymerase chain reaction was used to detect PERV and porcine mitochondrial DNA.…”