{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T12:37:10Z","timestamp":1793191030838,"version":"4.5.0"},"reference-count":18,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82400891"],"award-info":[{"award-number":["82400891"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82260154"],"award-info":[{"award-number":["82260154"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Academic Enhancement Support Program of Hainan Medical University","award":["XSTS2025161"],"award-info":[{"award-number":["XSTS2025161"]}]},{"name":"Y.W. is supported in part by the National Key Research and Development Program of China","award":["2023YFC3404304"],"award-info":[{"award-number":["2023YFC3404304"]}]},{"name":"the Hainan Provincial Science and Technology Talent Innovation Project","award":["KJRC2023B08"],"award-info":[{"award-number":["KJRC2023B08"]}]},{"name":"H.H. is supported in part by the Academic Enhancement Support Program of Hainan Medical University","award":["XSTS2025029"],"award-info":[{"award-number":["XSTS2025029"]}]},{"name":"the Hainan Provincial Natural Science Foundation of China","award":["326MS0417"],"award-info":[{"award-number":["326MS0417"]}]},{"name":"the Hainan Provincial High-Level Foreign Experts Program","award":["G20250218019E"],"award-info":[{"award-number":["G20250218019E"]}]},{"name":"the National Foreign Experts Program of China","award":["S20250233"],"award-info":[{"award-number":["S20250233"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>Genetically engineered porcine red blood cells (pRBCs) are emerging as a potential supplementary source of oxygen-carrying cells for transfusion medicine. Triple-knockout (TKO) pigs lacking major carbohydrate xenoantigens, including Gal, Neu5Gc, and Sd(a), have substantially reduced human antibody binding in vitro, and additional expression of human protective molecules such as CD55 and CD47 may further improve compatibility. However, the translational development of pRBC xenotransfusion is now constrained less by donor engineering alone than by the absence of an appropriate in vivo evaluation model. Old World nonhuman primates have historically served as essential preclinical models in xenotransplantation, but their cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH)-positive background and natural antibody repertoires may exaggerate immune barriers to TKO pRBCs that are not fully representative of humans. New World nonhuman primates, brain-dead human models, and eventually carefully regulated early-phase human studies each offer distinct advantages and limitations. In this Commentary, we argue that pRBC xenotransfusion requires a purpose-specific translational framework rather than reliance on a single preclinical model. Such a framework should integrate standardized compatibility testing, in vitro human assays, animal-based safety stress-testing, and, where ethically and legally feasible, short-term human reference models.<\/jats:p>","DOI":"10.1177\/09636897261477939","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T06:23:14Z","timestamp":1786083794000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Rethinking preclinical models for genetically engineered porcine red blood cell xenotransfusion"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3896-9788","authenticated-orcid":false,"given":"Xiayu","family":"Lei","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital of Hainan Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4179-7365","authenticated-orcid":false,"given":"Hidetaka","family":"Hara","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Hainan Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Hainan Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Hainan Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2019.01.003"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101113"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00130"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/trf.18116"},{"issue":"3","key":"e_1_3_7_6_2","first-page":"422","article-title":"Study on the safety and efficacy of micro-perfusion device for preserving isolated porcine limbs","volume":"17","author":"Li P","year":"2026","unstructured":"Li P, Mi Z, Li S, et al. Study on the safety and efficacy of micro-perfusion device for preserving isolated porcine limbs. 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StatPearls","author":"Basavarajegowda A","year":"2026","unstructured":"Basavarajegowda A, Zubair M, Shastry S. Pretransfusion Testing. StatPearls. Treasure Island (FL, 2026."},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12595"}],"container-title":["Cell Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09636897261477939","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/09636897261477939","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09636897261477939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T08:16:21Z","timestamp":1786263381000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/09636897261477939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":18,"alternative-id":["10.1177\/09636897261477939"],"URL":"https:\/\/doi.org\/10.1177\/09636897261477939","relation":{},"ISSN":["0963-6897","1555-3892"],"issn-type":[{"value":"0963-6897","type":"print"},{"value":"1555-3892","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"article-number":"09636897261477939"}}