Background: Xenotransplantation using porcine cells, tissues or organs is a promising method to alleviate the shortage of donated cadaveric human organs. Cross-species transmission of an infectious agent from the pig graft to the recipient, hepatic impact caused by an instant blood-mediated reaction, chronic over-immunosuppression and long-term potential infectious risk are the main concerns regarding xenotransplantation. Therefore, we designed a clinical trial to evaluate a biosafety system based on the principle of Changsha Communique for porcine islet xenotransplantation.
Methods: Based on current WHO guidelines and the existing pathogen list for designated pathogen-free (DPF) animals, we designed our updated DPF pathogen screening list. We had selectively inbred a Xiang pig herd for 12 years and confirmed their PERV-C free status and, most recently, their DPF status (Xeno-1). We here in report a clinical trial of ten adult patients (9 M:1 F) with type 1 diabetes who received DPF porcine islet xenotransplantation via the portal vein. Clinically accepted immunosuppressant protocol, tacrolimus, MMF, beletacept and autologous Tregs, were used for the recipients. The recipients were observed for follow-up biosafety evaluations such as infectious signs, microbiological detection, liver function, immunocytes and cytokines as the time schedule post-Tx. The recipients and their spouse were also examined the transmission of porcine endogenous retroviruses (PERV) and the micro-chimerism using PCR and cross-species infection monitoring.  
Results: PERV-C negative DPF donor piglets were certified in China by CFDA. All recipients and their spouse were minimal 1 year monitoring and up to 5 years. No cross-species pathogen infections and no PERV transmission were observed, and no severe transplant-related side effects were observed. Mild liver function damage was found post transplantation, but recover to normal within 28 days. We did not negatively alter the cytokine and immune responses in patients at 12 months’ post-islet xenotransplantation monitoring. The metabolic outcome improved, and hypoglycemic episodes decreased in all recipients. The exogenous insulin requirement decreased by an average of 45%, and the HbA1c decreased by 22.5% in recipients who received 11,400 ± 1828 IEQ/kg (n=4) at one year post transplantation.
Conclusion: This first-in-the-world pilot clinical trial for xenotransplantation biosafety system evaluation of fresh neonatal porcine islets demonstrates that validated DPF PERV-C-free pigs are safe from biohazard risks and transmission and are a valuable donor source of tissue for xenotransplantation. Our data demonstrate that this therapy is safe and efficacious, and these findings provide an important basis for future xenotransplantation studies.