{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T23:04:50Z","timestamp":1786489490835,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2U01AI090956\u201011"],"award-info":[{"award-number":["2U01AI090956\u201011"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Porcine islet xenotransplantation is limited by the availability of clinically applicable immunosuppressive regimens. We tested four depletional induction strategies and maintenance regimens in a non\u2010human primate (NHP) islet xenotransplant model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Genetically modified or wild\u2010type neonatal porcine islets were transplanted via portal vein infusion in diabetic NHPs. Induction consisted of rhesus anti\u2010thymocyte globulin (rhATG) (Group 1,\n                      <jats:italic>n<\/jats:italic>\n                      = 4), anti\u2010CD4 monoclonal antibody (mAb, Group 2,\n                      <jats:italic>n<\/jats:italic>\n                      = 3), or human anti\u2010thymocyte globulin (huATG) tocilizumab (Groups 3 and 4;\n                      <jats:italic>n<\/jats:italic>\n                      = 3 and\n                      <jats:italic>n<\/jats:italic>\n                      = 4, respectively). Maintenance consisted of B7 (Groups 1\u20133) or anti\u2010CD154 (Group 4) costimulation blockade, tacrolimus transitioned to sirolimus (sirolimus only in Group 4), and mycophenolate mofetil. Xenografts were monitored for blood glucose and porcine c\u2010peptide.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median graft survivals were &lt;14 days (Group 1), &lt;14 days (Group 2), 99 days (Group 3), and 119 days (Group 4). Insulin independence was achieved in one animal in Group 4. Graft survival significantly correlated with islet dose &gt;40,000 IEQ\/kg. Rejection was predominately CD3\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell mediated. Selective depletion of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells led to increased proliferation of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and CD8\n                      <jats:sup>+<\/jats:sup>\n                      infiltrates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Induction with huATG\/tocilizumab and maintenance with 5c8 led to the best functional outcomes. CD4 T\u2010cell depletion with anti\u2010CD4 mAb induced compensatory CD8 T\u2010cell proliferation and graft infiltration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/xen.70108","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T15:46:07Z","timestamp":1768578367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Report of Four Depletional Induction Strategies in Non\u2010Human Primate Islet Xenotransplantation"],"prefix":"10.1111","volume":"33","author":[{"given":"Meghan","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2456-7672","authenticated-orcid":false,"given":"Qimeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6787-3725","authenticated-orcid":false,"given":"Joseph","family":"Ladowski","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Anwar","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2340-0918","authenticated-orcid":false,"given":"Isabel","family":"DeLaura","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Tunbridge","sequence":"additional","affiliation":[{"name":"Department of Nephrology Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunrong","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Nephrology Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan D.","family":"Kirk","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"},{"name":"Department of Integrative Immunobiology Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"National Diabetes Statistics Report","author":"Close D. 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