{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:21:32Z","timestamp":1790173292178,"version":"4.1.0"},"reference-count":67,"publisher":"American Society for Clinical Investigation","issue":"20","funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["R01-HL085416 to JSP"],"award-info":[{"award-number":["R01-HL085416 to JSP"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["WMS as well as UL1-TR000142"],"award-info":[{"award-number":["WMS as well as UL1-TR000142"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["T32-DK007276 to JM"],"award-info":[{"award-number":["T32-DK007276 to JM"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,17]]},"abstract":"<jats:p>\n                    Tissue engineering may address organ shortages currently limiting clinical transplantation. Off-the-shelf engineered vascularized organs will likely use allogeneic endothelial cells (ECs) to construct microvessels required for graft perfusion. Vasculogenic ECs can be differentiated from committed progenitors (human endothelial colony-forming cells or HECFCs) without risk of mutation or teratoma formation associated with reprogrammed stem cells. Like other ECs, these cells can express both class I and class II major histocompatibility complex (MHC) molecules, bind donor-specific antibody (DSA), activate alloreactive T effector memory cells, and initiate rejection in the absence of donor leukocytes. CRISPR\/Cas9-mediated dual ablation of \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    -microglobulin and class II transactivator (CIITA) in HECFC-derived ECs eliminates both class I and II MHC expression while retaining EC functions and vasculogenic potential. Importantly, dually ablated ECs no longer bind human DSA or activate allogeneic CD4\n                    <jats:sup>+<\/jats:sup>\n                    effector memory T cells and are resistant to killing by CD8\n                    <jats:sup>+<\/jats:sup>\n                    alloreactive cytotoxic T lymphocytes in vitro and in vivo. Despite absent class I MHC molecules, these ECs do not activate or elicit cytotoxic activity from allogeneic natural killer cells. These data suggest that HECFC-derived ECs lacking MHC molecule expression can be utilized for engineering vascularized grafts that evade allorejection.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.129739","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T12:00:32Z","timestamp":1568721632000},"source":"Crossref","is-referenced-by-count":33,"title":["Progenitor-derived human endothelial cells evade alloimmunity by CRISPR\/Cas9-mediated complete ablation of MHC expression"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-1893","authenticated-orcid":true,"given":"Jonathan","family":"Merola","sequence":"first","affiliation":[{"name":"Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1902-5876","authenticated-orcid":true,"given":"Melanie","family":"Reschke","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Science, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5941-8805","authenticated-orcid":true,"given":"Richard W.","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingfeng","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2143-417X","authenticated-orcid":true,"given":"Susann","family":"Spindler","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Baltazar","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Manes","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7476-9822","authenticated-orcid":true,"given":"Francesc","family":"Lopez-Giraldez","sequence":"additional","affiliation":[{"name":"Yale Center for Genome Analysis and Department of Genetics, Yale University, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1775-965X","authenticated-orcid":true,"given":"Laura G.","family":"Bracaglia","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Science, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2687-0712","authenticated-orcid":true,"given":"Catherine","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Kirkiles-Smith","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Mark","family":"Saltzman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Science, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7227-2887","authenticated-orcid":true,"given":"Gregory T.","family":"Tietjen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Tellides","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5990-1071","authenticated-orcid":true,"given":"Jordan S.","family":"Pober","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2019,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199408113310606"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1210159"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706043162314"},{"issue":"Suppl 1","key":"B4","first-page":"6","article-title":"Organ shortage: Can we decrease the demand?","volume":"15","author":"Stephan","year":"2017","journal-title":"Exp Clin Transplant"},{"key":"B5","doi-asserted-by":"crossref","unstructured":"[No authors listed]. OPTN\/SRTR 2016 Annual Data Report. US Department of Health and Human Services. https:\/\/srtr.transplant.hrsa.gov\/annual_reports\/2016_ADR_Preview.aspx Accessed September 19, 2019","DOI":"10.1111\/ajt.15272"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5302.964"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3048"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.231"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3889"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2017.10.024"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05930615"},{"issue":"119","key":"B12","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1038\/ki.2010.419","article-title":"The pathology of chronic allograft dysfunction","author":"Racusen","year":"2010","journal-title":"Kidney Int Suppl"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002972"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181e065de"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000258730.75137.39"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.7.4397"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.10.5146"},{"issue":"12","key":"B18","doi-asserted-by":"crossref","first-page":"7022","DOI":"10.4049\/jimmunol.162.12.7022","article-title":"Human vascular endothelial cells favor clonal expansion of unusual alloreactive CTL","volume":"162","author":"Biedermann","year":"1999","journal-title":"J Immunol"},{"issue":"1","key":"B19","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.85293","article-title":"Blocking MHC class II on human endothelium mitigates acute rejection","volume":"1","author":"Abrahimi","year":"2016","journal-title":"JCI Insight"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.09.006"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.306290"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199304000-00046"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747050"},{"issue":"6","key":"B24","first-page":"2019","article-title":"Sublytic concentrations of the membrane attack complex of complement induce endothelial interleukin-8 and monocyte chemoattractant protein-1 through nuclear factor-kappa B activation","volume":"150","author":"Kilgore","year":"1997","journal-title":"Am J Pathol"},{"issue":"3","key":"B25","first-page":"953","article-title":"The membrane attack complex of complement induces interleukin-8 and monocyte chemoattractant protein-1 secretion from human umbilical vein endothelial cells","volume":"149","author":"Kilgore","year":"1996","journal-title":"Am J Pathol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199811150-00019"},{"issue":"4","key":"B27","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.4049\/jimmunol.163.4.2267","article-title":"Pretransplant frequency of donor-specific, IFN-gamma-producing lymphocytes is a manifestation of immunologic memory and correlates with the risk of posttransplant rejection episodes","volume":"163","author":"Heeger","year":"1999","journal-title":"J Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/319675a0"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2004.07.028"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903474106"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-11-319194"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.150242297"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.5.3020"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.11.7488"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13834"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199906270-00014"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1084\/jem.155.1.31"},{"issue":"8669","key":"B38","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S0140-6736(89)90951-3","article-title":"Effect of graft perfusion with two CD45 monoclonal antibodies on incidence of kidney allograft rejection","volume":"2","author":"Brewer","year":"1989","journal-title":"Lancet"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5954"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2012.11.003"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.88"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174077"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.10.004"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74337"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.18.6949"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10467"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1948.0026"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2858"},{"issue":"1\u20132","key":"B49","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/pr.2017.231","article-title":"Tissue regeneration using endothelial colony-forming cells: promising cells for vascular repair","volume":"83","author":"Banno","year":"2018","journal-title":"Pediatr Res"},{"issue":"1","key":"B50","first-page":"10","article-title":"Circulating and tissue resident endothelial progenitor cells","volume":"229","author":"Basile","year":"2014","journal-title":"J Cell Physiol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0190-2"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/stem.471"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.10.110"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-010-9157-y"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4951"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.147256"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2010.0024"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.05.061"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2754-3"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.2.457"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-372946"},{"issue":"10","key":"B62","first-page":"1534","article-title":"Human umbilical cord mesenchymal stem cells derived from Wharton\u2019s jelly differentiate into insulin-producing cells in vitro","volume":"124","author":"Wang","year":"2011","journal-title":"Chin Med J"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5682fje"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp120"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1621"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(01)00297-2"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20162143"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/129739\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:22:46Z","timestamp":1779193366000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/129739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,17]]},"references-count":67,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2019,10,17]]},"published-print":{"date-parts":[[2019,10,17]]}},"alternative-id":["10.1172\/jci.insight.129739"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.129739","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,17]]},"article-number":"e129739"}}