Clinical Trial for Safety of Porcine Islet Xenotransplantation From PERV‐C Free DPF Donor Piglets in Patients With Type 1 Diabetes

BACKGROUND: Xenotransplantation of porcine cells, tissues or organs offers a promising strategy to address the critical shortage of human donor organs. However, cross-species pathogen transmission, instant blood-mediated inflammatory reaction (IBMIR)-related liver injury, chronic over-immunosuppression, and long-term safety remain major challenges in porcine islet xenotransplantation. In this study, we performed a clinical trial aimed to evaluate the biosafety of neonatal porcine islet xenotransplantation in patients with type 1 diabetes. METHODS: Ten recipients were assigned to two groups receiving non-encapsulated neonatal islet cell clusters via the jugular-hepatic-portal vein at mean doses of 6354 ± 835 IEQ/kg and 11 600 ± 1100 IEQ/kg, respectively. Donor pigs originated from a highly inbred, PERV-C-negative colony reared in designated pathogen-free (DPF) conditions, with rigorous pathogen and PERV screening. Immunosuppression included mycophenolate mofetil, tacrolimus, belatacept, and autologous regulatory T-cell therapy, combined with tocilizumab. Continuous low-dose heparin was infused via a portal vein catheter was used for 7 days as anticoagulation therapy. Recipients and spouses were monitored for over 5 years, with 7 followed for more than 10 years. RESULTS: No PERV transmission or transplant-related infections were detected in any recipient or contact during long-term follow-up. The procedure was safe and well-tolerated, with only transient liver function and coagulation changes and mild adverse events. Both groups showed reduced exogenous insulin requirements and markedly lower hypoglycemia incidence, with better glucose control in the higher-dose group. CONCLUSION: This study demonstrates that DPF PERV-C-free neonatal porcine islet xenotransplantation is biologically safe and partially effective, supporting its value as a reliable donor source and foundational platform for advancing clinical islet xenotransplantation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03162237.