{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:24:39Z","timestamp":1791915879022,"version":"4.3.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Science and Technology Project of Yunnan Province","award":["202102AA100054"],"award-info":[{"award-number":["202102AA100054"]}]},{"name":"Major Science and Technology Project of Yunnan Province","award":["202102AA310047"],"award-info":[{"award-number":["202102AA310047"]}]},{"name":"Basic Strengthening Program","award":["2023-JCJQ-ZD-118-00\/173"],"award-info":[{"award-number":["2023-JCJQ-ZD-118-00\/173"]}]},{"name":"Xingdian Talent Support Program","award":["XDYC-KJLJ-2022-0004"],"award-info":[{"award-number":["XDYC-KJLJ-2022-0004"]}]},{"name":"Major Science and Technology Project, Yunnan Province","award":["202102AA310047"],"award-info":[{"award-number":["202102AA310047"]}]},{"name":"Major Science and Technology Project, Yunnan Province","award":["202102AA100054"],"award-info":[{"award-number":["202102AA100054"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFA0110700"],"award-info":[{"award-number":["2019YFA0110700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Xenotransplantation has entered the clinical phase in an effort to address the global organ shortage. However, recent clinical studies have revealed that current xenografts from gene-edited (GE) pigs still pose a risk of immune rejection and biosafety concerns. In this study, we successfully produced a large batch of 582 GE cloned (GEC) pigs with 10-(GTKO\/CMAHKO\/\u03b24GalNT2KO\/hCD46\/ hCD55\/hCD59\/hTBM\/hCD39\/hEPCR\/hCD47) gene edits via gene editing and somatic cell cloning technologies, and successfully obtained the F1 generation. Phenotypic characterization of 10-GEC pigs revealed the deletion of three xenoantigens and the expression of seven human transgenes across various tissues. Digital droplet polymerase chain reaction and whole-genome sequencing revealed two copies of hCD46\/hCD55\/hCD59\/hTBM\/hCD39 and one copy of hEPCR\/hCD47 in the pig genome with minimal off-target effects or damage to the porcine functional genes. The validation results showed that 10-GEC pigs could effectively inhibit attacks from human antibodies, complement and macrophages on porcine endothelial cells,\u00a0and alleviated coagulation abnormalities between pigs and humans. Large-scale screening of pathogens revealed no evidence of 47 pathogens, including cytomegalovirus, in our 10-GEC pigs. Kidney, heart and liver xenografts from these 10-GEC pigs were transplanted into nonhuman primates (NHPs), which worked normally without hyperacute rejection (HAR). Among NHPs, the heart and liver orthotopic transplant recipients survived for 3 and 4 days, respectively, while the two kidney transplant recipients survived for 23 and 16 days, respectively. Pathological analysis showed interstitial hemorrhage and fibrosis, cellular hyperplasia with minor antibodies and complement deposition, but significantly reduced infiltration of CD68+ macrophages in 10-GEC pig kidney xenografts. In summary, we successfully produced specific pathogen-free 10-GEC donor pigs that resulted in effective mitigation of immune rejection upon multiorgan transplantation to NHPs.<\/jats:p>","DOI":"10.1093\/procel\/pwaf075","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T11:39:45Z","timestamp":1755949185000},"page":"1002-1016","source":"Crossref","is-referenced-by-count":12,"title":["Specific pathogen free ten gene-edited donor pigs for xenotransplantation"],"prefix":"10.1093","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6665-3360","authenticated-orcid":false,"given":"Kaixiang","family":"Xu","sequence":"first","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University , Kunming 650201 ,","place":["China"]},{"name":"Yunnan Province Xenotransplantation Engineering Research Center, Yunnan Agricultural University , Kunming 650201 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Kunming 650201 ,","place":["China"]},{"name":"Yunnan Province Xenotransplantation Engineering Research Center, Yunnan Agricultural University , Kunming 650201 ,","place":["China"]},{"name":"College of Veterinary Medicine, Yunnan Agricultural University , Kunming 650201 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaoxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University , Kunming 650201 ,","place":["China"]},{"name":"Yunnan Province Xenotransplantation Engineering Research Center, Yunnan Agricultural University , Kunming 650201 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazar Ali Mohammed Ali","family":"Siddig","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University , Kunming 650201 ,","place":["China"]},{"name":"Yunnan Province Xenotransplantation Engineering Research Center, Yunnan Agricultural University , Kunming 650201 ,","place":["China"]},{"name":"Faculty of Animal Science and Technology, Yunnan Agricultural University , Kunming 650201 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8364-6389","authenticated-orcid":false,"given":"Muhammad Ameen","family":"Jamal","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University , Kunming 650201 ,","place":["China"]},{"name":"Yunnan Province Xenotransplantation Engineering Research Center, Yunnan Agricultural University , Kunming 650201 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aqiang","family":"Mao","sequence":"additional","affiliation":[{"name":"Yunnan Province Key Laboratory for Porcine Gene 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