{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:53:34Z","timestamp":1792180414495,"version":"4.4.0"},"reference-count":72,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1105401"],"award-info":[{"award-number":["2022YFA1105401"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Xenotransplantation utilizing pig donors offers a promising solution to organ shortages, but immune incompatibilities across species remain a major challenge. Current reliance on porcine primary fibroblasts for genome editing is limited by low inefficiency in complex gene editing and difficulties in immunophenotyping edited cells. In this study, we demonstrate that porcine expanded potential stem cells (pEPSCs), derived from preimplantation embryos, provide a robust and versatile platform for generating donor cells for xenotransplantation. These pluripotent cells can differentiate into both embryonic and extraembryonic lineages, maintain genetic stability through multiple edits, and enable precise genome modifications. We performed multiple gene knockouts in pEPSCs targeting key immune rejection genes and precisely inserted a genetic cassette to facilitate streamlined introduction of human cDNAs via cassette exchange. The engineered pEPSCs retained their pluripotency and stability even after multiple rounds of genome editing. When differentiated into endothelial cells, they exhibited high immunogenicity, serving as a rapid and quantitative platform for immune response assessment. Importantly, the edited endothelial cells exhibited substantially reduced immunogenicity, confirming the functional impact of the genetic modifications. Although we have not yet generated live pigs from these gene\u2010edited pEPSCs via somatic cell nuclear transfer (SCNT), our findings establish pEPSCs as a novel and improved platform for generating genetically engineered pig donors and for functionally evaluating genetic modifications, thereby advancing the prospects of xenotransplantation.<\/jats:p>","DOI":"10.1111\/xen.70161","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T07:57:27Z","timestamp":1787299047000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Porcine Expanded Potential Stem Cells as a Versatile Platform for Multiplex Genome Editing and Immunophenotyping in Xenotransplantation"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0725-0286","authenticated-orcid":false,"given":"Yiyi","family":"Xuan","sequence":"first","affiliation":[{"name":"InnoHK Centre for Translational Stem Cell Biology  Hong Kong Science Park, Hong Kong Special Administrative Region China"},{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong, Hong Kong Special Administrative Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Shatin, Hong Kong Special Administrative Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xining","family":"Wang","sequence":"additional","affiliation":[{"name":"InnoHK Centre for Translational Stem Cell Biology  Hong Kong Science Park, Hong Kong Special Administrative Region China"},{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong, Hong Kong Special Administrative Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1532-4863","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Petersen","sequence":"additional","affiliation":[{"name":"FLI, Institute of Farm Animal Genetics  Mariensee Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5774-9678","authenticated-orcid":false,"given":"Pentao","family":"Liu","sequence":"additional","affiliation":[{"name":"InnoHK Centre for Translational Stem Cell Biology  Hong Kong Science Park, Hong Kong Special Administrative Region China"},{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong, Hong Kong Special Administrative Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"H. 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