{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:05:48Z","timestamp":1777662348266,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T00:00:00Z","timestamp":1500249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"crossref","award":["973 Program; 2015CB554100"],"award-info":[{"award-number":["973 Program; 2015CB554100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Xijing Hospital Disciplines Boosting Project","award":["XJZT12M09"],"award-info":[{"award-number":["XJZT12M09"]}]},{"name":"Xijing Hospital Disciplines Boosting Project","award":["XJZT13Z01"],"award-info":[{"award-number":["XJZT13Z01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pig\u2010to\u2010nonhuman primate orthotopic liver xenotransplantation is often accompanied by thrombocytopenia and coagulation disorders. Furthermore, the release of cytokines can trigger cascade reactions of coagulation and immune attacks within transplant recipients. To better elucidate the process of inflammation in liver xenograft recipients, we utilized a modified heterotopic auxiliary liver xenotransplantation model for xeno\u2010immunological research. We studied the cytokine profiles and the relationship between cytokine levels and xenograft function after liver xenotransplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Appropriate donor and recipient matches were screened using complement\u2010dependent cytotoxicity assays. Donor liver grafts from \u03b11,3\u2010galactosyltransferase gene\u2010knockout (<jats:styled-content style=\"fixed-case\">GTKO<\/jats:styled-content>) pigs or <jats:styled-content style=\"fixed-case\">GTKO<\/jats:styled-content> pigs additionally transgenic for human <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>47 (<jats:styled-content style=\"fixed-case\">GTKO<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>47) were transplanted into Tibetan macaques via two different heterotrophic auxiliary liver xenotransplantation procedures. The cytokine profiles, hepatic function, and coagulation parameters were monitored during the clinical course of xenotransplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Xenograft blood flow was stable in recipients after heterotopic auxiliary transplantation. A Doppler examination indicated that the blood flow speed was faster in the hepatic artery (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>) and hepatic vein (<jats:styled-content style=\"fixed-case\">HV<\/jats:styled-content>) of xenografts subjected to the modified Sur <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010abdominal aorta+<jats:styled-content style=\"fixed-case\">HV<\/jats:styled-content>\u2010inferior vena cava) procedure than in those subjected to our previously reported Sur I (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010splenic artery+<jats:styled-content style=\"fixed-case\">HV<\/jats:styled-content>\u2010left renal vein) procedure. Tibetan macaques receiving liver xenografts did not exhibit severe coagulation disorders or immune rejection. Although the recipients did suffer from a rapid loss of platelets, this loss was mild. In blood samples dynamically collected after xenotransplantation (post\u2010Tx), dramatic increases in the levels of monocyte chemoattractant protein 1, interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20108, granulocyte\u2010macrophage colony\u2010stimulating factor, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106, and interferon gamma\u2010induced protein 10 were observed at 1\u00a0hour post\u2010Tx, even under immunosuppression. We further confirmed that the elevation in individual cytokine levels was correlated with the onset of graft damage. Finally, the release of cytokines might contribute to leukocyte infiltration in the xenografts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Here, we established a modified auxiliary liver xenotransplantation model resulting in near\u2010normal hepatic function. Inflammatory cytokines might contribute to early damage in liver xenografts. Controlling the systemic inflammatory response of recipients might prevent early post\u2010Tx graft dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12321","type":"journal-article","created":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T08:18:44Z","timestamp":1500279524000},"source":"Crossref","is-referenced-by-count":34,"title":["Cytokine profiles in Tibetan macaques following \u03b1\u20101,3\u2010galactosyltransferase\u2010knockout pig liver xenotransplantation"],"prefix":"10.1111","volume":"24","author":[{"given":"Zhuochao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery Xijing Hospital Fourth Military Medical University  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Xijing Hospital Fourth Military Medical University  Xi'an 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