{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:36:58Z","timestamp":1753879018411,"version":"3.41.2"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T00:00:00Z","timestamp":1655510400000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009037","name":"Science and Technology Research Partnership for Sustainable Development","doi-asserted-by":"publisher","award":["JPMJSA1506"],"award-info":[{"award-number":["JPMJSA1506"]}],"id":[{"id":"10.13039\/501100009037","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770621","82070638"],"award-info":[{"award-number":["81770621","82070638"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The human\u2010to\u2010rat hematopoietic stem cell transplantation (HSCT) model is rare, unlike its human\u2010to\u2010mouse counterpart. The rat models are desired, especially in areas of physiology, toxicology, and pharmacology. In addition to lymphocytes, macrophages are also considered to be important for xenotransplantation. We generated a rat xenotransplantation model to prove the role of macrophages as a xenotransplantation barrier.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunodeficiency in SRG rats, which are Sprague\u2013Dawley (SD) rats lacking <jats:italic>Rag2<\/jats:italic> and <jats:italic>Il2rg<\/jats:italic>, was confirmed by flow cytometry and spleen immunostaining. Human umbilical cord blood was collected after scheduled cesarean section at the University of Tsukuba Hospital. Cord blood mononuclear cells (CB\u2010MNCs) were transplanted into the SRG rats administered several injections of clodronate liposome (CL), which cause macrophage depletion. Survival of human cells was observed by flow cytometry. Rat macrophage phagocytosis assay was performed to check the species\u2010specific effects of rat macrophages on injected human\/rat blood cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SRG rats were deficient in T\/B\/NK cells. Without CL pretreatment, human CB\u2010MNCs were removed from SRG rats within 7\u00a0hours after transplantation. The rats pretreated with CL could survive after transplantation. Prolonged survival for more than 4\u00a0weeks was observed only following a one\u2010time CL injection. Rat macrophages had a species\u2010specific potential for the phagocytosis of human blood cells in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In human\u2010to\u2010rat HSCT, the short period of early macrophage control, leading to macrophage immunotolerance, is important for engraftment. The generated model can be useful for the creation of future xenotransplantation models or other clinical research.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12702","type":"journal-article","created":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T05:11:25Z","timestamp":1624079485000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The evidence of a macrophage barrier in the xenotransplantation of human hematopoietic stem cells to severely immunodeficient rats"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2630-3072","authenticated-orcid":false,"given":"Kinji","family":"Furuya","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Faculty of Medicine University of Tsukuba Tsukuba 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Medicine University of Tsukuba Tsukuba Japan"},{"name":"Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine and School of Biotechnology and Health Sciences Wuyi University Jiangmen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludi","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences University of Chinese Academy of Science Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoaki","family":"Furuta","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Faculty of Medicine University of Tsukuba Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of 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