@article{781,
  keywords = {Blood-Air Barrier, Cells, Cultured, Coculture Techniques, Drug development, Drug Discovery, Endothelial Cells, Epithelial Cells, Evidence-Based Medicine, Fibrinolytic Agents, Humans, Lab-On-A-Chip Devices, Microfluidic Analytical Techniques, Microvessels, Patient Safety, Pulmonary Alveoli, Risk Assessment, Signal Transduction, Thrombosis, Translational Research, Biomedical},
  author = {A. Jain and R. Barrile and A. D. van der Meer and A. Mammoto and T. Mammoto and K. De Ceunynck and O. Aisiku and M. A. Otieno and C. S. Louden and G. A. Hamilton and R. Flaumenhaft and D. E. Ingber},
  title = {Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for Assessment of Therapeutics},
  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.},
  year = {2018},
  journal = {Clinical Pharmacology and Therapeutics},
  volume = {103},
  pages = {332-340},
  month = {2018-02},
  issn = {1532-6535},
  doi = {10.1002/cpt.742},
  language = {eng},
}