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Morozov, V.A.* ; Ludwig, S.* ; Ludwig, B. ; Rotem, A.* ; Barkai, U.* ; Bornstein, S.R. ; Denner, J.*

Islet cell transplantation from Gottingen minipigs to cynomolgus monkeys: Analysis of virus safety.

Xenotransplantation 23, 320-327 (2016)
Open Access Green as soon as Postprint is submitted to ZB.
BackgroundXenotransplantation using pig cells, tissues or organs may be associated with the transmission of porcine zoonotic micro-organisms. Hepatitis E virus (HEV), porcine cytomegalovirus (PCMV) and porcine endogenous retroviruses (PERVs) are potentially zoonotic micro-organisms which do not show clinical symptoms in pigs and which are due to the low expression level difficult to detect. Gottingen Minipigs (GoMP) are often used for biomedical investigations and they are well characterized concerning the presence of numerous bacteria, fungi, viruses and parasites and therefore may be used for islet cell transplantation. MethodsIslet cells derived from three GoMP were transplanted into four healthy, non-diabetic cynomolgus monkeys using a macroencapsulation device. PCR, nested PCR, real-time PCR, real-time RT-PCR and Western blot analyses were used to estimate the presence of PERV, PCMV and HEV in the donors and recipients. ResultsUsing sensitive detection methods, no HEV was found in the donor pigs and in the pig islet cell preparations. Antibodies against PERV, PCMV and HEV were not found in all cynomolgus monkeys with exception of one monkey showing an immune response against HEV. Using real-time PCR, no PCMV and HEV were found in the sera of all monkeys. ConclusionAlthough the donor islet cells and the recipients were negative for HEV using PCR and Western blot analysis, in one recipient, antibodies against HEV were found, indicating infection in a single case. All recipients were negative for antibodies against PERV, and all were negative for PCMV, indicating absence of infection. As HEV was not detected in the donor pig before transplantation, a more complex and regular screening of the animals using highly sensitive methods is required to avoid virus transmission.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Hepatitis E Virus ; Islet Cell Transplantation ; Non-human Primates ; Porcine Cytomegalovirus ; Porcine Herpesviruses ; Viral Safety; Porcine Endogenous Retroviruses; Hepatitis-e Virus; Nonhuman-primates; Liver Sausage; Xenotransplantation; Infection; Pig; Cytomegalovirus; Immunosuppression; Transmission
ISSN (print) / ISBN 0908-665X
e-ISSN 1399-3089
Quellenangaben Volume: 23, Issue: 4, Pages: 320-327 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken, NJ
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)