Long-term follow-up for the microbiological safety of clinical microencapsulated neonatal porcine islet transplantation.

ABSTRACT

Enrollment in three clinical trials for microencapsulated neonatal porcine islet xenotransplantation to treat unstable type 1 diabetic patients concluded in November 2014. In this study, we report a long-term follow-up assessment of microbiological safety for these trials. Thirty-eight type 1 diabetic patients received microencapsulated neonatal porcine islet transplants. Islets were isolated and prepared from the pancreata of New Zealand (NZ) based designated pathogen-free (DPF) pigs under GMP conditions. Blood samples of thirty-six patients were collected from 5 to 7 years post-first transplant and were tested by real-time PCR for porcine circovirus-1 (PCV1), porcine circovirus-2 (PCV2), porcine lymphotropic herpesvirus 1 (PLHV1), porcine lymphotropic herpesvirus 2 (PLHV2), and porcine cytomegalovirus (PCMV). To detect porcine endogenous retrovirus (PERV), specific real-time PCR and product enhanced reserve transcriptase (PERT) assays were performed. PCV1, PCV2, PLHV1, PLHV2, PCMV, PERV, and reverse transcriptase (RT) activity remained undetected in all tested samples indicating no viral transmission. Except for one patient that died due to complications unrelated to the transplant, there were no significant adverse events. Microbiological safety was demonstrated for microencapsulated neonatal porcine islet xenotransplantation from 5-7 years post-transplantation consistent with earlier reports.