{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T08:52:00Z","timestamp":1792054320540,"version":"4.4.0"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":44,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Long term xenografts often fail in association with evidence of coagulation pathway dysregulation, which may be caused in part by the inefficient binding of inactivated protein C (PC) to porcine thrombomodulin (TBM). This study evaluates the effect of human TBM (hTBM) expression by genetically modified pig endothelium on human platelet activation, adhesion, and aggregation within a dynamic in vitro xenoperfusion model. Porcine aortic endothelial cells (PAECs) with a variety of genetic modifications and immortalized human coronary endothelial cells (HCECs) (\n                    <jats:italic>n<\/jats:italic>\n                    = 9) were cultured to confluence in microfluidic channels and perfused for one hour with human whole blood stained with 0.5\u00a0mM Calcein to visualize thrombosis formation. After one hour of perfusion, platelet adhesion (as percent surface area coverage) and aggregation (fluorescence intensity) were significantly reduced in association with human APC (hAPC) pretreatment of GTKO, and with DKO.hCD55.hTBM or 10\u2010GE ECs relative to GT\/DKO \u00b1 hCD55 ECs. Fold change in frequency of activated (CD62P+) platelets in channel effluent was significantly decreased in association with GTKO+hAPC (1.5 \u00b1 0.03\n                    <jats:italic>p<\/jats:italic>\n                    = 0.01,\n                    <jats:italic>n<\/jats:italic>\n                    = 6), and DKO.hCD55.hTBM (1.6 \u00b1 0.03\n                    <jats:italic>p<\/jats:italic>\n                    = 0.02,\n                    <jats:italic>n<\/jats:italic>\n                    = 12) or 10\u2010GE ECs (1.3 \u00b1 0.04\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.0001,\n                    <jats:italic>n<\/jats:italic>\n                    = 9) relative to GT\/DKO \u00b1 hCD55 ECs (1.8 \u00b1 0.07,\n                    <jats:italic>n<\/jats:italic>\n                    = 8). No significant difference was observed between DKO.hCD55.hTBM and GTKO+hAPC. We conclude that, under conditions mimicking microcirculatory flow, hTBM expression confers anti\u2010thrombotic effects comparable to those with hAPC pretreatment of GTKO ECs. Consequently, hTBM expression is a promising method to inhibit platelet dysregulation in xenotransplant models.\n                  <\/jats:p>","DOI":"10.1111\/xen.70176","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T08:43:13Z","timestamp":1792053793000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression of Human Thrombomodulin by Porcine Endothelium Attenuates Thrombus Formation and Platelet Activation in a Dynamic Shear Flow Model"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4809-4260","authenticated-orcid":false,"given":"Megan","family":"Dufault","sequence":"first","affiliation":[{"name":"Center For Transplantation Sciences Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Columbia Vagelos College of Physicians and Surgeons  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayed\u2010Amir","family":"Sanatkar","sequence":"additional","affiliation":[{"name":"Center For Transplantation Sciences Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3314-3716","authenticated-orcid":false,"given":"Zahra","family":"Habibabady","sequence":"additional","affiliation":[{"name":"Center For Transplantation Sciences Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Diaz","sequence":"additional","affiliation":[{"name":"Center For Transplantation Sciences Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4478-8442","authenticated-orcid":false,"given":"Jonathan","family":"Schulz","sequence":"additional","affiliation":[{"name":"Center For Transplantation Sciences Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Cardiovascular Surgery University Hospital of Mainz  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3029-7987","authenticated-orcid":false,"given":"Cinthia","family":"Gomes Lucas","sequence":"additional","affiliation":[{"name":"National Swine Resource and Research Center  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9386-0004","authenticated-orcid":false,"given":"Kevin D.","family":"Wells","sequence":"additional","affiliation":[{"name":"National Swine Resource and Research Center  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9959-108X","authenticated-orcid":false,"given":"Kristin M.","family":"Whitworth","sequence":"additional","affiliation":[{"name":"National Swine Resource and Research Center  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ayares","sequence":"additional","affiliation":[{"name":"Revivicor, Inc.  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Richard N.","family":"Pierson","sequence":"additional","affiliation":[{"name":"Center For Transplantation Sciences Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of Cardiac Surgery, Department of Surgery Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20103089.2004.00155.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070672"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890\u2010199901150\u201000004"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890\u2010200011150\u201000010"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000131167.21930.b8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710791233706"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20106143.2008.02210.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202401128R"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071699"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102006\u201009\u2010003004"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12828"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155580"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001188"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12133"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16876"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12408"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.70115"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2024.07.022"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12729"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102004\u201010\u20103985"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100017200"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00003.2010"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102141.2009.08020.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.124.3_suppl.26s"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200803\u2010419OC"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103083441001"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD004388.pub6"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27506"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12712"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12557"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529\u2010024\u201003505\u2010z"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0049\u20103848(01)00392\u20109"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/labmed\/lmad022"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20106143.2005.00792.x"},{"issue":"4","key":"e_1_2_10_36_1","doi-asserted-by":"crossref","first-page":"S145","DOI":"10.1016\/j.healun.2020.01.1069","article-title":"Human Thrombomodulin Transgene Expression Prevents Intracardiac Thrombus in Life Supporting Pig\u2010to\u2010Baboon Cardiac Xenotransplantation","volume":"39","author":"Goerlich C. 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