AN69 hollow fiber membrane will reduce but not abolish the risk of transmission of porcine endogenous retroviruses.
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 supematant 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.
Pakhomov
Oleg
O
Biology of Nutrition, Paris 5 University Faculty of Pharmacy, France.
Martignat
Lionel
L
Honiger
Jiri
J
Clémenceau
Béatrice
B
Saï
Pierre
P
Darquy
Sylviane
S
D000818:Animals; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D020077:Endogenous Retroviruses / Q000235:genetics / Q000472:pathogenicity*; D015750:Genes, gag; D006801:Humans; D016381:Islets of Langerhans Transplantation; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D008815:Mice, Inbred Strains; D016133:Polymerase Chain Reaction; D012192:Retroviridae Infections / Q000517:prevention & control / Q000635:transmission*; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects*
D004272:DNA, Mitochondrial; D004279:DNA, Viral; D008567:Membranes, Artificial