{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:24:08Z","timestamp":1788323048271,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,3,17]],"date-time":"2017-03-17T00:00:00Z","timestamp":1489708800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21\u00a0A1074844"],"award-info":[{"award-number":["R21\u00a0A1074844"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AI068642"],"award-info":[{"award-number":["U01 AI068642"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI090959"],"award-info":[{"award-number":["U19 AI090959"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RR012317\u201009"],"award-info":[{"award-number":["RR012317\u201009"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Genetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310\u00a0days, but graft survival &gt;30\u00a0days has been unusual until recently.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Donor pigs (n=4) were on an \u03b11,3\u2010galactosyltransferase gene\u2010knockout (GTKO)\/human complement regulatory protein (CD46) background (GTKO\/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein. Two baboons received a kidney from a six\u2010gene pig (GroupA) and two from a three\u2010gene pig (GroupB). Immunosuppressive therapy was identical in all four cases and consisted of anti\u2010thymoglobulin (ATG)+anti\u2010CD20mAb (induction) and anti\u2010CD40mAb+rapamycin+corticosteroids (maintenance). Anti\u2010TNF\u2010\u03b1 and anti\u2010IL\u20106R mAbs were administered to reduce the inflammatory response. Baboons were followed by clinical\/laboratory monitoring of immune\/coagulation\/inflammatory\/physiological parameters. At biopsy or euthanasia, the grafts were examined by microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The two GroupA baboons remained healthy with normal renal function &gt;7 and &gt;8\u00a0months, respectively, but then developed infectious complications. However, no features of a consumptive coagulopathy, eg, thrombocytopenia and reduction of fibrinogen, or of a protein\u2010losing nephropathy were observed. There was no evidence of an elicited anti\u2010pig antibody response, and histology of biopsies taken at approximately 4, 6, and 7\u00a0months and at necropsy showed no significant abnormalities. In contrast, both GroupB baboons developed features of a consumptive coagulopathy and required euthanasia on day 12.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The combination of (i) a graft from a specific six\u2010gene genetically modified pig, (ii) an effective immunosuppressive regimen, and (iii) anti\u2010inflammatory therapy prevented immune injury, a protein\u2010losing nephropathy, and coagulation dysfunction for &gt;7\u00a0months. Although the number of experiments is very limited, our impression is that expression of human endothelial protein C receptor (\u00b1CD55) in the graft is important if coagulation dysregulation is to be avoided.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/xen.12293","type":"journal-article","created":{"date-parts":[[2017,3,17]],"date-time":"2017-03-17T04:53:16Z","timestamp":1489726396000},"source":"Crossref","is-referenced-by-count":204,"title":["Immunological and physiological observations in baboons with life\u2010supporting genetically engineered pig kidney grafts"],"prefix":"10.1111","volume":"24","author":[{"given":"Hayato","family":"Iwase","sequence":"first","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Hara","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Ezzelarab","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh  Pittsburgh PA USA"},{"name":"Center for Kidney Transplantation Second Affiliated Hospital of the University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh  Pittsburgh PA USA"},{"name":"Department of General Surgery Second Xiangya Hospital of the Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingsi","family":"Gao","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh  Pittsburgh PA USA"},{"name":"Center for Kidney Transplantation Second Affiliated Hospital of the University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh  Pittsburgh PA USA"},{"name":"Department of General Surgery First Hospital of Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Long","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Kidney Transplantation Second Affiliated Hospital of the University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Cassano","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Resources University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Klein","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Resources University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Phelps","sequence":"additional","affiliation":[{"name":"Revivicor  Blacksburg VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ayares","sequence":"additional","affiliation":[{"name":"Revivicor  Blacksburg VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinav","family":"Humar","sequence":"additional","affiliation":[{"name":"Thomas E. 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