{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:18:40Z","timestamp":1792804720944,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,5,17]],"date-time":"2018-05-17T00:00:00Z","timestamp":1526515200000},"content-version":"am","delay-in-days":307,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2017,7,14]],"date-time":"2017-07-14T00:00:00Z","timestamp":1499990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["N66001\u201011\u20101\u20104180"],"award-info":[{"award-number":["N66001\u201011\u20101\u20104180"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["HR0011\u201013\u2010C\u20100025"],"award-info":[{"award-number":["HR0011\u201013\u2010C\u20100025"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008897","name":"Janssen Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>Pulmonary thrombosis is a significant cause of patient mortality; however, there are no effective <jats:italic>in vitro<\/jats:italic> models of thrombi formation in human lung microvessels that could also assess therapeutics and toxicology of antithrombotic drugs. Here, we show that a microfluidic lung alveolus\u2010on\u2010a\u2010chip lined by human primary alveolar epithelium interfaced with endothelium and cultured under flowing whole blood can be used to perform quantitative analysis of organ\u2010level contributions to inflammation\u2010induced thrombosis. This microfluidic chip recapitulates <jats:italic>in vivo<\/jats:italic> responses, including platelet\u2010endothelial dynamics and revealed that lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis by activating the alveolar epithelium, rather than acting directly on endothelium. This model is also used to analyze inhibition of endothelial activation and thrombosis due to a protease activated receptor\u20101 (PAR\u20101) antagonist, demonstrating its ability to dissect complex responses and identify antithrombotic therapeutics. Thus, this methodology offers a new approach to study human pathophysiology of pulmonary thrombosis and advance drug development.<\/jats:p>","DOI":"10.1002\/cpt.742","type":"journal-article","created":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T01:42:44Z","timestamp":1495071764000},"page":"332-340","source":"Crossref","is-referenced-by-count":313,"title":["Primary Human Lung Alveolus\u2010on\u2010a\u2010chip Model of Intravascular Thrombosis for Assessment of Therapeutics"],"prefix":"10.1111","volume":"103","author":[{"given":"A","family":"Jain","sequence":"first","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University Boston Massachusetts USA"},{"name":"Vascular Biology Program and Department of Surgery Boston Children's Hospital and Harvard Medical School Boston Massachusetts USA"},{"name":"Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Biomedical Engineering, Dwight Look College of Engineering Texas A&amp;M University College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Barrile","sequence":"additional","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University Boston Massachusetts USA"},{"name":"Cedars\u2010Sinai Medical Center Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AD","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University Boston Massachusetts USA"},{"name":"MIRA Institute for Biomedical Technology and Technical Medicine University of Twente Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Mammoto","sequence":"additional","affiliation":[{"name":"Vascular Biology Program and Department of Surgery Boston Children's Hospital and Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Mammoto","sequence":"additional","affiliation":[{"name":"Vascular Biology Program and Department of Surgery Boston Children's Hospital and Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"De Ceunynck","sequence":"additional","affiliation":[{"name":"Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Aisiku","sequence":"additional","affiliation":[{"name":"Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MA","family":"Otieno","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutical Research and Development Pre\u2010Clinical Development and Safety Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CS","family":"Louden","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutical Research and Development Pre\u2010Clinical Development and Safety Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GA","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Emulate Inc. Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Flaumenhaft","sequence":"additional","affiliation":[{"name":"Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DE","family":"Ingber","sequence":"additional","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering Harvard University Boston Massachusetts USA"},{"name":"Vascular Biology Program and Department of Surgery Boston Children's Hospital and Harvard Medical School Boston Massachusetts USA"},{"name":"Harvard John A. Paulson School of Engineering and Applied Sciences Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,14]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12047"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-11-0666"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0241TR"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2008.09.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201107-1312ED"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-5231(05)70283-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.12703\/P6-38"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00010.2008"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2014.12.002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-3692(15)51873-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012414-040418"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2989"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-12-027698"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0753-3322(00)88861-7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e31823a088c"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-199903000-00004"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183752"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2014.12.050"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.02.049"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1188302"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004249"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910170110"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3697"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-010-0182-4"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054680"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt110"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4064"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10544-016-0095-6"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0801082"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.225334"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-550319"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm782"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3109\/09537104.2012.709653"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-012-0658-5"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10176"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-550335"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.006213"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2012.12.020"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11373-004-8170-z"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13061"},{"key":"e_1_2_9_41_1","doi-asserted-by":"crossref","unstructured":"DeCeunynck K.E.P.et al.A chemical APC mimetic protects endothelium from thromboinflammatory injury. Presented at the 58th American Society of Hematology Annual Meeting & Exposition San Diego CA 3\u20136 December2016. Abstract 3835.","DOI":"10.1182\/blood.V128.22.3835.3835"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-09-599910"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10334-010-0203-1"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bioeng.1.1.299"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-fluid-010814-014513"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-012-0557-9"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201240109"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.4818837"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58753"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126797"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.742","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.742","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.742","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/cpt.742","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.742","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:35:27Z","timestamp":1699364127000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,14]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1002\/cpt.742"],"URL":"https:\/\/doi.org\/10.1002\/cpt.742","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,14]]}}}