{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:59:26Z","timestamp":1790614766025,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T00:00:00Z","timestamp":1629504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01AI045897"],"award-info":[{"award-number":["P01AI045897"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nephrotic syndrome is a common complication of pig\u2010to\u2010baboon kidney xenotransplantation (KXTx) that adversely affects outcomes. We have reported that upregulation of CD80 and down\u2010regulation of SMPDL\u20103b in glomeruli have an important role in the development of proteinuria following pig\u2010to\u2010baboon KXTx. Recently we found induced expression of human CD47 (hCD47) on endothelial cells and podocytes isolated from hCD47 transgenic (Tg) swine markedly reduced phagocytosis by baboon and human macrophages. These observations led us to hypothesize that transplanting hCD47 Tg porcine kidneys could overcome the incompatibility of the porcine CD47\u2010baboon SIRP\u03b1 interspecies ligand\u2010receptor interaction and prevent the development of proteinuria following KXTx.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten baboons received pig kidneys with vascularized thymic grafts (<jats:italic>n<\/jats:italic>\u00a0=\u00a08) or intra\u2010bone bone marrow transplants (<jats:italic>n<\/jats:italic>\u00a0=\u00a02). Baboons were divided into three groups (A, B, and C) based on the transgenic expression of hCD47 in GalT\u2010KO pigs. Baboons in Group A received kidney grafts with expression of hCD47 restricted to glomerular cells (<jats:italic>n<\/jats:italic>\u00a0=\u00a02). Baboons in Group B received kidney grafts with high expression of hCD47 on both glomerular and tubular cells of the kidneys (<jats:italic>n<\/jats:italic>\u00a0=\u00a04). Baboons in Group C received kidney grafts with low\/no glomerular expression of hCD47, and high expression of hCD47 on renal tubular cells (<jats:italic>n<\/jats:italic>\u00a0=\u00a04).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Consistent with this hypothesis, GalT\u2010KO\/hCD47 kidney grafts with high expression of hCD47 on glomerular cells developed minimal proteinuria. However, high hCD47 expression in all renal cells including renal tubular cells induced an apparent destructive inflammatory response associated with upregulated thrombospondin\u20101. This response could be avoided by a short course of weekly anti\u2010IL6R antibody administration, resulting in prolonged survival without proteinuria (mean 170.5 days from 47.8 days).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Data showed that transgenic expression of hCD47 on glomerular cells in the GalT\u2010KO donor kidneys can prevent xenograft nephropathy, a significant barrier for therapeutic applications of xenotransplantation. The ability to prevent nephrotic syndrome following KXTx overcomes a critical barrier for future clinical applications of KXTx.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12708","type":"journal-article","created":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T20:33:40Z","timestamp":1629578020000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Expression of human CD47 in pig glomeruli prevents proteinuria and prolongs graft survival following pig\u2010to\u2010baboon xenotransplantation"],"prefix":"10.1111","volume":"28","author":[{"given":"Kazuhiro","family":"Takeuchi","sequence":"first","affiliation":[{"name":"Columbia Center for Translational Immunology Department of Medicine Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Ariyoshi","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology Department of Medicine Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Analytic Human Pathology Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Okumura","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology Department of Medicine Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Cara\u2010Fuentes","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension University of Colorado Denver  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela E.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension University of Colorado Denver  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Pomposelli","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology Department of Medicine Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironosuke","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology Department of Medicine Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennan","family":"Boyd","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology Department of Medicine Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilrukshi K.","family":"Ekanayake\u2010Alper","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology Department of 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