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However, cross\u2010species pathogen transmission, instant blood\u2010mediated inflammatory reaction (IBMIR)\u2010related liver injury, chronic over\u2010immunosuppression, and long\u2010term 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ten recipients were assigned to two groups receiving non\u2010encapsulated neonatal islet cell clusters via the jugular\u2010hepatic\u2010portal vein at mean doses of 6354\u00a0\u00b1\u00a0835\u00a0IEQ\/kg and 11\u00a0600\u00a0\u00b1\u00a01100\u00a0IEQ\/kg, respectively. Donor pigs originated from a highly inbred, PERV\u2010C\u2010negative colony reared in designated pathogen\u2010free (DPF) conditions, with rigorous pathogen and PERV screening. Immunosuppression included mycophenolate mofetil, tacrolimus, belatacept, and autologous regulatory T\u2010cell therapy, combined with tocilizumab. Continuous low\u2010dose 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No PERV transmission or transplant\u2010related infections were detected in any recipient or contact during long\u2010term follow\u2010up. The procedure was safe and well\u2010tolerated, 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\u2010dose group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that DPF PERV\u2010C\u2010free 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov identifier: NCT03162237<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/xen.70148","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T07:52:34Z","timestamp":1781682754000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical Trial for Safety of Porcine Islet Xenotransplantation From PERV\u2010C Free DPF Donor Piglets in Patients With Type 1 Diabetes"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8315-9927","authenticated-orcid":false,"given":"Xiaoqian","family":"Ma","sequence":"first","affiliation":[{"name":"The Institute for Cell Transplantation and Gene Therapy The Third Xiangya Hospital of Central South University  Changsha China"},{"name":"Engineering and Technology Research Center for Xenotransplantation of Human Province  Changsha China"},{"name":"National Health Commission Key Laboratory of Translational Research on Transplantation Medicine  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The Third Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicong","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Sci\u2010Tech Inno Center for Infection &amp; 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