Heart-and-vessel-on-a-chip for lipid-lowering therapy.

Here this project aims to develop a novel human heart-on-chip model for improved metabolism and fatty acid utilisation, comparable to the human heart in vivo. In collaboration with a private partner, they have optimised and standardised the production of microfluidic chips, which will enable functional analysis and evaluation of fatty acid metabolism and screening of drugs in a versatile, standardised heart-on-chip platform.

Cardiovascular diseases are the number one cause of death worldwide, claiming 17.9 million deaths per year. Most deaths are due to ischemic heart disease, which is mostly caused by narrowing of the coronary artery because of atherosclerosis (accumulation of cholesterol). Current lipid-lowering therapies are reducing the risk of cardiovascular events but are still far from ideal since current experimental models are not fully recapitulating the human situation. This stresses the urgent need for creating human-based models for a better understanding of cardiovascular disease and for drug screening.

To create a human heart-on-chip in vitro model, they implemented human-induced pluripotent stem cells that are differentiated to specialised cardiac muscle and vascular cells, followed by formation of three-dimensional cardiac tissues. The objective was to generate cardiac tissues that are more comparable to the human heart and are capable of fatty acid uptake and utilisation and in combination with improved functional analysis. In order to achieve this, they engineered a microfluidic chip that allows the formation of these tissues and functional evaluation.

In conclusion, this project has generated human cardiovascular tissues that are able to take up fatty acids. By optimising the fatty acid composition, they observed improved cardiac function (increased contractility, calcium handling) and activation of molecular pathways that are associated with cardiac maturation. Moreover, the heart-on-chip model is compatible with further optimisation, standardisation of cardiac tissues in an automated microfluidic platform for identification of novel drugs, including lipid-lowering therapeutics.