{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:51:51Z","timestamp":1792180311767,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Combined renal and islet xenotransplantation could provide a durable treatment for end\u2010stage diabetic nephropathy. In this feasibility\u2010focused study, we evaluated two complementary approaches for clinical translation: (1) pre\u2010vascularized composite islet\u2013kidney (I\u2013K) grafts and (2) sequential islet\u2010after\u2010kidney xenotransplantation with vascularized thymic lobe (VTL) co\u2010transplantation as an adjunct immune tolerance strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Composite I\u2013K grafts were generated in nine MHC\u2010matched, minor\u2010antigen\u2010mismatched miniature swine pairs by implanting adult porcine islets beneath the renal capsule of juvenile kidney donors followed by pre\u2010vascularization under tacrolimus\u2010based immunosuppression. Separately, three baboons underwent GalTKO.hCD55 kidney and VTL xenotransplantation, followed by streptozocin\u2010induced diabetes and intraportal adult porcine islet infusion from a separate donor. Renal\/metabolic function, porcine C\u2010peptide, histology, and immune profiling were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Composite I\u2013K grafts demonstrated limited islet survival with peri\u2010islet inflammation on histology at the graft preparation stage and were not advanced to pig\u2010to\u2010NHP xenotransplantation in this study. Sequential islet\u2010after\u2010kidney transplantation restored insulin\u2010independent euglycemia in all recipients. Porcine C\u2010peptide was detectable in the long\u2010term survivor with intrahepatic insulin\u2010positive islets at necropsy. Infection\u2010associated thrombotic microangiopathy limited survival in two animals; in the 180\u2010day survivor, anti\u2010porcine hypo\u2010responsiveness and evidence of thymopoiesis within the VTL graft were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this limited series, sequential islet\u2010after\u2010kidney xenotransplantation restored metabolic control and represents a promising translational strategy for diabetic nephropathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/xen.70153","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T12:36:45Z","timestamp":1783341405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Islet and Kidney Xenotransplantation for Diabetic Nephropathy: Investigation of Pre\u2010Vascularized Composite Grafts versus Sequential Islet\u2010After\u2010Kidney Transplantation in a Pig\u2010to\u2010Nonhuman Primate Model of Xenotransplantation"],"prefix":"10.1111","volume":"33","author":[{"given":"Alexander C.","family":"Schulick","sequence":"first","affiliation":[{"name":"School of Medicine Johns Hopkins University, MD  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Eisenson","sequence":"additional","affiliation":[{"name":"School of Medicine Johns Hopkins University, MD  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WeiLi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine Johns Hopkins University, MD  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxing","family":"Cui","sequence":"additional","affiliation":[{"name":"MedStar Georgetown University Hospital  Washington DC 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