Xenotransplantation of pig islet cells is a promising alternative for the treatment of diabetes with
insulin and may help to prevent numerous late complications such as
blindness and
amputation. First encouraging results using porcine islets have been reported in preclinical animal models as well in the first clinical trial in New Zealand. The goal of this manuscript is to examine the
biological safety of a second trial performed in Argentina, specifically in regards to the transmission of porcine endogenous retroviruses (PERVs) using improved detection methods As in the first trial encapsulated islet cells from the well-characterised Auckland Island pigs were used. The animals were not genetically modified. The islet cells were transplanted in eight human recipients using a modified clinical protocol. Sera taken at different time points after
transplantation (up to 55 weeks) were screened for the presence of
antibodies against PERV
proteins by Western blot analysis using
viral antigens from highly purified virus particles. Positive sera obtained by immunization with recombinant PERV
proteins were used as control sera. In none of the patients
antibodies against PERV were detected, indicating the absence of
infection. In parallel at different time points (up to 113 weeks) white blood cells (WBC) have been tested for PERV
DNA, and WBC and plasma for PERV
RNA by real-time RT-PCR. All tests were negative. In addition, using primers detecting pig mitochondrial
cytochrome oxidase (COX) gene, patients were screened for microchimerism. In summary, the data are further evidence for the safety of pig islet cell
transplantation.