title: Islet cell transplantation from Göttingen minipigs to cynomolgus monkeys: analysis of virus safety.
abstract: Xenotransplantation 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. Göttingen Minipigs (GöMP) 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.
  
  
  
  Islet cells derived from three GöMP 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.
  
  
  
  Using 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.
  
  
  
  Although 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.
authors.affiliation: HIV and other Retroviruses, Robert Koch Institute, Berlin, Germany.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Morozov
authors.affiliation: Department of Visceral- Thorax- and Vascular Surgery, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ludwig
authors.affiliation: Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany.|Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden and DZD- German Centre for Diabetes Research, Dresden, Germany.|Centre for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ludwig
authors.affiliation: Beta-O2 Technologies Ltd., Rosh-Haain, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Rotem
authors.affiliation: Beta-O2 Technologies Ltd., Rosh-Haain, Israel.
authors.forename: Uriel
authors.initials: U
authors.lastname: Barkai
authors.affiliation: Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany.|Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden and DZD- German Centre for Diabetes Research, Dresden, Germany.|Centre for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.|Department of Endocrinology and Diabetes, King's College, London, UK.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.affiliation: HIV and other Retroviruses, Robert Koch Institute, Berlin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Denner
mesh_terms: D000818:Animals; D004267:DNA Viruses / Q000235:genetics; D020077:Endogenous Retroviruses; D016752:Hepatitis E virus; D007515:Islets of Langerhans / Q000821:virology*; D016381:Islets of Langerhans Transplantation / Q000379:methods; D008252:Macaca fascicularis / Q000821:virology*; D013552:Swine; D013556:Swine, Miniature / Q000821:virology*; D014183:Transplantation, Heterologous / Q000379:methods
keywords: hepatitis E virus; islet cell transplantation; non-human primates; porcine cytomegalovirus; porcine herpesviruses; viral safety