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High levels of elicited anti\u2010pig IgG may develop if the adaptive immune response is not prevented by adequate immunosuppressive therapy, resulting in activation and injury of the vascular endothelium. The transplantation of organs and cells from pigs that do not express the important Gal antigen (\u03b11,3\u2010galactosyltransferase gene\u2010knockout [\n                    <jats:styled-content style=\"fixed-case\">GTKO<\/jats:styled-content>\n                    ] pigs) and express one or more human complement\u2010regulatory proteins (\n                    <jats:styled-content style=\"fixed-case\">hCRP<\/jats:styled-content>\n                    , e.g.,\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    46,\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    55), when combined with an effective costimulation blockade\u2010based immunosuppressive regimen, prevents early antibody\u2010mediated and cellular rejection. However, low levels of anti\u2010non\u2010Gal antibody and innate immune cells and\/or platelets may initiate the development of a thrombotic microangiopathy in the graft that may be associated with a consumptive coagulopathy in the recipient. This pathogenic process is accentuated by the dysregulation of the coagulation\u2010anticoagulation systems between pigs and primates. The expression in\n                    <jats:styled-content style=\"fixed-case\">GTKO<\/jats:styled-content>\n                    \/\n                    <jats:styled-content style=\"fixed-case\">hCRP<\/jats:styled-content>\n                    pigs of a human coagulation\u2010regulatory protein, for example, thrombomodulin, is increasingly being associated with prolonged pig graft survival in non\u2010human primates. Initial clinical trials of islet and corneal xenotransplantation are already underway, and trials of pig kidney or heart transplantation are anticipated within the next few years.\n                  <\/jats:p>","DOI":"10.1111\/xen.12219","type":"journal-article","created":{"date-parts":[[2016,1,27]],"date-time":"2016-01-27T03:01:34Z","timestamp":1453863694000},"page":"83-105","source":"Crossref","is-referenced-by-count":137,"title":["The pathobiology of pig\u2010to\u2010primate xenotransplantation: a historical review"],"prefix":"10.1111","volume":"23","author":[{"given":"David K.C.","family":"Cooper","sequence":"first","affiliation":[{"name":"The Thomas E. Starzl Transplantation Institute University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed B.","family":"Ezzelarab","sequence":"additional","affiliation":[{"name":"The Thomas E. 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