Introduction: We have conducted clinical trials of encapsulated neonatal porcine islet transplantation under regulatory approval (1,2). To obtain the regulatory approval, we established designate pathogen free (DPF) porcine herds and patients’ monitoring system (3).　Under this system we followed the patients and showed the microbiological safety for 5-7 years post transplantation (4). In this study, we further followed the patient to evaluate the long-term microbiological safety.

Methods: Blood samples were obtained from 13 patients who received the encapsulated neonatal porcine islet transplantation 8.0 to 11.0 years ago (average 10.0 years). Buffy coats were separated from blood samples for PCR assay as previously described (3). Porcine Circovirus 2 (PCV2), Porcine cytomegalovirus (PCMV), porcine lymphotropic herpesvirus1 (PLHV1), PLHV2, porcine endogenous retrovirus (PERV) DNA, PERV RNA were assessed. In addition, pig mitochondrial cytochrome oxidase (COX) RNA and DNA were assessed for microchimerism.

Results: All samples showed negative for PCV2, PCMV, PLHV1, PLHV2, PERV DNA, and PERV RNA. These outcomes are consistent with our previous findings.
COX RNA and DNA were negative in all samples indicated no microchimerism occurred.

Discussion/Conclusion: To initiate clinical trial of islet xenotransplantation, we established DPF pig herd which exclude possible pathogens. However, all pigs have PERVs in their genome, therefore, PERVs exist even in the DPF herd. In addition, PLHV and PCMV are known to act as latent infection agents which could be activated in any time. With the reasons, long-term follow up of such viruses are necessary to monitor biological safety after xenotransplantation. In this study, we confirmed our previous findings of safety of encapsulated neonatal porcine islet transplantation.
In conclusion, none of the patients suffered from xenozoonoses for long-term (average 10years) after encapsulated neonatal porcine islet transplantation.
 

References
1. Matsumoto S, Tan P, Baker J, et al. Clinical porcine islet xenotransplantation under comprehensive regulation. Transplant Proc 2014; 46: 1992.
2. Matsumoto S, Abalovich A, Wechsler C, et al. Clinical benefit of islet xenotransplantation for the treatment of type 1 diabetes. EBioMedicine 2016; 12: 255.
3. Wynyard S, Nathu D, Garkavenko O, et al. Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand. Xenotransplantation 2014; 21:309.
4. Matsumoto S, Wynyard S, Giovannangelo M, et al. Long-term follow-up for the microbiological safety of clinical encapsulated neonatal porcine islet transplantation. Xenotransplantation 2020; 27; e12631.