title: Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand.
abstract: BACKGROUND
  Xenotransplantation using pig cells, tissues, or organs may be associated with the transmission of porcine microorganisms and the development of zoonoses. Among all porcine microorganisms porcine endogenous retroviruses (PERVs) represent a special risk because they are integrated in the genome of all pigs and able to infect human cells. In previous preclinical and retrospective clinical trials of xenotransplantation, no transmission of PERV was observed. The first clinical trial of (alginate-encapsulated) porcine islet cell transplantation in New Zealand, which was approved by the New Zealand Government as an open-label phase I/IIa safety/efficacy trial, offers the possibility to analyze microbiological safety in a prospective clinical study.
  
  
  METHODS
  Before the trial started, a multilevel testing strategy was used to screen for 26 microorganisms in donor pigs of the Auckland Island strain and the islet cell preparations used for treatment. Donor testing was performed using molecular methods including multiplex real-time PCR. Blood samples from 14 pig islet cell recipients were also investigated by molecular biological methods at weeks 1, 4, 8, 12, 24, and 52 post-transplant for the transmission of porcine microorganisms. Sera were also monitored at these time points for antibodies against PERVs.
  
  
  RESULTS
  Beginning in 2009, fourteen patients with severe unaware hypoglycemia were treated with one of four different dosages of alginate-encapsulated porcine islets ranging from 5000-20,000 islet equivalents delivered in a single dose. No transmission of either PERVs or other porcine microorganisms was detected by PCR and immunological methods.
  
  
  CONCLUSIONS
  These findings support previous results and strongly indicate the safety of xenotransplantation as performed here.
authors.affiliation: Living Cell Technologies, Manukau, New Zealand.
authors.forename: Shaun
authors.initials: S
authors.lastname: Wynyard
authors.forename: Divya
authors.initials: D
authors.lastname: Nathu
authors.forename: Olga
authors.initials: O
authors.lastname: Garkavenko
authors.forename: Joachim
authors.initials: J
authors.lastname: Denner
authors.forename: Robert
authors.initials: R
authors.lastname: Elliott
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000379:methods*; D009520:New Zealand; D061214:Patient Safety; D011446:Prospective Studies; D012307:Risk Factors; D034421:Sus scrofa / Q000276:immunology / Q000382:microbiology / Q000821:virology; D014019:Tissue Donors; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000379:methods*; D015047:Zoonoses / Q000517:prevention & control / Q000635:transmission
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral
keywords: diabetes; high resolution melting; pancreatic islets; porcine endogenous retrovirus; porcine viruses; xenoses; zoonoses