The Dutch Research Council (NWO) has awarded Dr. Ben Johnson (reNEW Leiden) an Open Competition ENW-XS grant. Johnson will use the grant to develop a stem cell-based model to simulate human heart attacks in a petri dish. The new model could lead to a better understanding of how the heart responds following the attack and the discovery of novel medications for patients in the future.
Cardiovascular diseases are a leading cause of death worldwide. Heart attacks are a major contributor to this mortality and only limited treatment options are currently available for this disease. Despite this need, the discovery of new, effective therapies has remained challenging due to a lack of reliable and representative human heart attack models. Ben Johnson, Postdoc in the labs of AI Richard Davis and PI Christine Mummery, will now use this grant to develop such a model system.
The labs of Davis and Mummery focus on modeling cardiac diseases using human induced pluripotent stem cells (hiPSCs). Johnson: “We have ample experience in modeling cardiac diseases and previously generated cardiac microtissues [3D cell models] from hiPSCs. These microtissues not only contain cardiomyocytes, the contractile cell of the heart, but also other cell types in the heart such as cardiac fibroblasts and cells of the vasculature. This makes them an ideal model to study cardiac diseases such as heart attacks in which multiple cell types play a role.”
In order to generate a model of a heart attack, the researcher will integrate a small population of genetically modified cardiomyocytes into the healthy microtissues. The genetically modified cardiomyocytes contain a so-called ‘kill-switch’ in their DNA. Johnson explains: “This ‘kill switch’ will allow us to consecutively induce inflammation and cell death in a small, localized region of the healthy microtissue, mimicking what occurs following a real heart attack. We aim to then use this model and study how the different cells in the heart react to this damage and explore methods to repair the cardiac damage.”
An ongoing reNEW project has developed methods for producing cardiac microtissues using robotics, and this system could therefore potentially be used for high-throughput drug screenings. Such a model therefore offers the possibility to identify new therapies for patients that suffer from a heart attack in the future.
In the NWO Open Competition ENW, researchers can apply individually or in collaboration for fundamental, curiosity-driven research in the fields of the NWO-Domain Science (ENW). These fields include earth sciences, astronomy, chemistry, computer science, life sciences, physics and mathematics. In total 28 projects were awarded. Read more here.