Thrombosis is the pathological formation of blood clots inside blood vessels, even in the absence of vascular injury or bleeding. Thrombosis is the result of a combination of blood-borne factors (e.g. genetic defects in platelets or coagulation factors), vessel wall dysfunction (e.g. chronic inflammation) and fluid dynamical effects (e.g. stasis or flow reversal in stenosed valves). Thrombosis in arteries is often associated with atherosclerosis and is a major cause of myocardial infarctions and stroke.
Thrombosis is currently studied mostly in mouse models and by using flow chambers in vitro. Both models have their limitations, mostly because they fail to mimic key aspects of human physiology and disease.
Organ-on-chip technology is changing the way we study thrombosis in the lab. We and others have previously performed proof-of-principle experiments that demonstrate that microfluidic chips can be used to unify the three major aspects of thrombosis – blood, vessel wall, fluid dynamics – in one controlled model, and that these models can be used to study the dynamics of a forming thrombus by live-cell microscopy.
In this project, we develop organ-on-chip models for thrombosis that include key aspects of thrombosis in specific patients or subsets of patients. We will develop a microfluidic chip that (1) is a direct representation of the blood vessel geometry of a specific patient, based on their angiography imaging data, (2) is covered with patient-specific endothelium that has been derived from patient stem cells, and (3) is perfused with patient blood samples. We will apply these patient-specific organ-on-chip models of thrombosis to understand and predict the risk of thrombosis for specific subsets of patients, as well as to evaluate drug and treatment efficacy for these patients.
For more information, please contact: