Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for Assessment of Therapeutics

Clinical Pharmacology and Therapeutics
A JainDonald E Ingber

Abstract

Pulmonary thrombosis is a significant cause of patient mortality; however, there are no effective in vitro 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-on-a-chip lined by human primary alveolar epithelium interfaced with endothelium and cultured under flowing whole blood can be used to perform quantitative analysis of organ-level contributions to inflammation-induced thrombosis. This microfluidic chip recapitulates in vivo responses, including platelet-endothelial 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-1 (PAR-1) 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.

References

Jan 15, 1976·International Journal of Cancer. Journal International Du Cancer·M LieberG Todaro
Mar 24, 1999·Current Opinion in Hematology·D A Andrews, P S Low
Apr 12, 2000·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·A Sagripanti, A Carpi
Oct 10, 2001·Clinics in Chest Medicine·R M TuderN F Voelkel
Oct 10, 2001·Clinics in Chest Medicine·P HerveG Simonneau
Nov 10, 2001·Annual Review of Biomedical Engineering·D M Wootton, D N Ku
Feb 22, 2007·Blood·Shaun P Jackson
Mar 11, 2008·Thrombosis and Haemostasis·Malgorzata WygreckaPhilipp Markart
Jul 16, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Gustavo Matute-BelloThomas R Martin
Aug 30, 2008·American Journal of Respiratory Cell and Molecular Biology·Fernando A BozzaGuy A Zimmerman
Aug 30, 2008·The New England Journal of Medicine·Bruce Furie, Barbara C Furie
Oct 22, 2008·Microvascular Research·James H Finigan
Jun 26, 2010·Science·Dongeun HuhDonald E Ingber
Oct 16, 2010·Annals of Biomedical Engineering·T ColaceS L Diamond
Mar 2, 2011·Disease Models & Mechanisms·Alastair G ProudfootMatthew Hind
Mar 12, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Brian C Cooley
Nov 3, 2011·American Journal of Respiratory and Critical Care Medicine·Michael J Cuttica, Roberto Machado
Nov 23, 2011·Anesthesia and Analgesia·Alisa S WolbergKellie R Machlus
Mar 31, 2012·Annals of Biomedical Engineering·Mathew H Flamm, S L Diamond
May 31, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ying ZhengAbraham D Stroock
Aug 10, 2012·Platelets·Erik WesteinJohan W M Heemskerk
Sep 25, 2012·Annals of Biomedical Engineering·Ryan R HansenKeith B Neeves
Oct 10, 2012·Annual Review of Physiology·Andrew S Weyrich, Guy A Zimmerman
Nov 2, 2012·Journal of Thrombosis and Haemostasis : JTH·G J GlasM Levi
Nov 9, 2012·Science Translational Medicine·Dongeun HuhDonald E Ingber
May 15, 2013·Cardiovascular Research·Judith M E M CosemansJohan W M Heemskerk
Aug 6, 2014·Nature Biotechnology·Sangeeta N Bhatia, Donald E Ingber
Jan 27, 2015·Annual Review of Pathology·Kambez H BenamDonald E Ingber
Feb 24, 2015·Journal of Vascular Surgery·Lauren D C CasaDavid N Ku
Apr 4, 2015·Rheumatic Diseases Clinics of North America·Marina Vivero, Robert F Padera
Jul 21, 2015·Journal of Thrombosis and Haemostasis : JTH·J HawigerJ Zienkiewicz
Aug 4, 2015·Annual Review of Fluid Mechanics·Aaron L Fogelson, Keith B Neeves
Jul 29, 2016·Biomedical Microdevices·Abhishek JainDonald E Ingber

❮ Previous
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Citations

Dec 21, 2017·American Journal of Respiratory and Critical Care Medicine·Kambez H BenamOliver Eickelberg
Jun 5, 2018·Lab on a Chip·Murat Cirit, Cynthia L Stokes
Jan 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Karen De CeunynckRobert Flaumenhaft
Nov 15, 2018·Micromachines·Juan Eduardo Sosa-HernándezHafiz M N Iqbal
Sep 29, 2018·The European Respiratory Journal·Konstantinos GkatzisSaverio Bellusci
Mar 12, 2019·Current Pharmaceutical Design·Yasamin A JodatSu R Shin
Feb 16, 2019·American Journal of Respiratory Cell and Molecular Biology·Simon J ClearySimon C Pitchford
Nov 15, 2019·Small·Kirsten Lee FetahNureddin Ashammakhi
Feb 23, 2020·Journal of Cardiovascular Translational Research·Emily A PinheiroPaul W Burridge
Feb 26, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pierfrancesco PagellaThimios A Mitsiadis
Jan 22, 2020·Annual Review of Analytical Chemistry·Olivier T GuenatFrançois Berthiaume
Jun 17, 2020·Biotechnology and Bioengineering·Milad RadiomYong Chen
Aug 22, 2020·Stem Cells Translational Medicine·Abbas ShafieeJason Brown
Jun 12, 2018·Biomicrofluidics·Janna Tenenbaum-KatanJosué Sznitman
Jan 8, 2020·Critical Reviews in Biotechnology·Jesus ShresthaMaliheh Ghadiri
Feb 11, 2020·Frontiers in Oncology·Mirna SwaydenJuan Iovanna
Jun 24, 2020·Micromachines·Neda AzizipourAbdellah Ajji
Jun 18, 2020·Frontiers in Bioengineering and Biotechnology·Jia-Wei YangGuan-Yu Chen
Aug 1, 2020·Micromachines·Joseph R Puryear IiiYongTae Kim
Jul 16, 2020·Materials·Liubov BakhchovaUlrike Steinmann
Sep 10, 2020·Frontiers in Bioengineering and Biotechnology·Rocio J Jimenez-ValdesKambez H Benam
Sep 20, 2020·Bioengineering·Vanessa AllwardtVirginia Pensabene
Jan 13, 2018·Biomaterials Science·James C H PoonThomas K Waddell
Jan 9, 2018·Annual Review of Pharmacology and Toxicology·Rachelle Prantil-BaunDonald E Ingber
Aug 10, 2018·Toxicology Research·Frank S BierkandtAndreas Luch
Nov 18, 2018·Journal of Cellular Physiology·Rahul MittalVasanti M Jhaveri
Sep 27, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Donald E Ingber
Jan 17, 2019·Nature Reviews. Cancer·Alexandra Sontheimer-PhelpsDonald E Ingber
Jul 19, 2018·Biomicrofluidics·Yusuf B ArıkAndries D van der Meer
May 20, 2018·Development·Donald E Ingber
Aug 6, 2020·Micromachines·Ungsig NamJessie S Jeon
Sep 27, 2018·Scientific Reports·Janick D StuckiOlivier T Guenat
Aug 8, 2020·Chemical Society Reviews·María Virumbrales-MuñozDavid J Beebe
Jul 11, 2020·Advanced Biosystems·Arbel Artzy-SchnirmanJosué Sznitman
Nov 12, 2020·American Journal of Physiology. Cell Physiology·Savannah R MosesJonathan W Song
Nov 27, 2020·Biotechnology and Bioengineering·Huaqi TangAlireza Mashaghi
Jun 25, 2020·Seminars in Cancer Biology·Amanda M ClarkAlan Wells

❮ Previous
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