To meet this challenge, the team used Organ-on-a-Chip (Organ Chip) technology developed at the Wyss Institute, which involves engineering microfluidic culture devices with two parallel channels separated by a porous extracellular-matrix-coated membrane. The key innovation in this new design relative to a previously described Lung-on-a-Chip is that the upper surface of the porous membrane is lined by primary human alveolar epithelial cells, and all sides of the lower vascular channel are coated with a layer of lung microvascular endothelium to accurately mimic human lung capillaries. Because thrombosis is perpetrated by platelets and other cells, the team perfused whole human blood through the lower endothelium-lined channel of the chip for the first time, while air was introduced into the upper channel. When an inflammatory stimulus was applied to the endothelial cells followed by perfusing whole blood, platelets clumped and formed blood clots on the surface of the endothelium.
With the disease model the researchers were able to test drugs.
As a next step, the team plans to continue their pulmonary thrombosis work by introducing mechanical forces that imitate breathing to the Chip and analyzing the role that immune cells such as neutrophils play in blood clot formation.
Original paper:
Abhishek Jain, Riccardo Barrile, Andries D. van der Meer, Akiko Mammoto, Tadanori Mammoto, Karen De Ceunvnck, Omozuanvbo Aisiku, Monicah A. Otieno, Calvert S. Louden, Geraldine A. Hamilton, Robert Flaumenhaft & Donald E. Ingber (2017): A primary human lung alveolus-on-a-chip model of intravascular thrombosis for assessment of therapeutics. Clinical Pharmacology & Therapeutics, 17. Mai 2017, DOI: 10.1002/cpt.742.
Source:
https://wyss.harvard.edu/pulmonary-thrombosis-on-a-chip-provides-new-avenue-for-drug-development/