“The microvessel-on-a-chip has been developed in line with 21st Century Toxicology and the drive to limit animal testing through the development of new physiologically relevant in vitro models,” said Dr. Carine Poussin, PMI. “While rodent models are commonly used to investigate the mechanisms of atherogenesis, we have now demonstrated the suitability of an alternative in vitro model in a real-world setting. The scalability of the microvessel-on-a-chip offers the potential to further develop the model for a range of mechanistic investigations of vascular diseases. This has important implications for a number of fields, including toxicological assessment, drug discovery, and precision medicine.” 

Researchers used the microvessel-on-a-chip to assess the impact of Tobacco Heating System (THS) 2.2 aerosol and cigarette smoke, in the form of aqueous extracts, on the adhesion of monocytic cells to the blood vessel wall. In addition to standard functional endpoints, various molecular endpoints were measured by high-content imaging. Exposure of microvessels to cigarette smoke triggered an inflammatory response that promoted an increase in the adhesion of monocytic cells to vessel walls as well as an increase in oxidative stress. In contrast, at the concentrations of cigarette smoke at which functional and molecular effects peaked, no significant effect was observed with THS 2.2 aerosol. It was necessary to increase the concentration of THS 2.2 aerosol by a factor of 14 to elicit similar effects. Taking all endpoints into consideration, the microvessel-on-a-chip model showed the potential of THS 2.2 aerosol to exert a significantly reduced impact on mechanisms that are known to lead to the development of atherosclerosis. THS 2.2 is a candidate reduced-risk product* being developed and assessed by PMI 

Not only does the microvessel-on-a-chip have the potential to reduce the need for animal testing in line with the 3Rs principle (replace, reduce, and refine the use of animals in research), it may also provide more accurate, detailed, and timely data. By using human tissues, organ-on-a-chip models avoid the challenges involved in translating the results observed in one species to another. In association with advances in molecular endpoint assessment and computational modelling, they can also help decrease the rate of clinical failure of new drugs and be used as a valuable tool for selection of precision medicine solutions. The data generated in this study are available on PMI’s data sharing platform INTERVALS at https://doi.org/10.26126/intervals.elcwt4.1.