Grant for studying the underlying principles of biological pacemakers
Many people suffer from a slow heartbeat. The natural pacemaker of the heart - the sinus node - then does not work properly. NWO Research programme XL (previous OC ENW-GROOT) has awarded the project 'Pacing the heart; studying the underlying principles of biological pacemakers' to elucidate the elementary principles and minimal requirements to assemble a functional pacemaker from human stem cells.
To identify these basic principles, the researchers take a novel approach by assessing conserved mechanisms of pacemaker tissue development and composition in evolutionary divergent species (fish, mouse) and use this knowledge to rebuild and optimize a cardiac pacemaker model in silico and in vitro from human pluripotent stem cells.
The consortium consists of experts in developmental biology, in human stem cell differentiation, tissue engineering and microfabrication, in mathematical modelling of tissue patterning, in cellular electrophysiology, and in the biochemistry of cellular interactions.
The consortium will generate mathematical simulation models to define the minimal requirements for the assembly of functional pacemaker-atrial tissues with input from the in vivo observations in fish and mouse. The predictions from the mathematical models will be used to assemble and test simplified pacemaker units on a chip using differentiated cells derived from human pluripotent stem cells.
In the future, they hope to use this knowledge to repair defective sinus nodes with gene therapy. The cultured pacemakers are useful in studies of slow heartbeat and in drug testing.
The five-year project started on September 1th, 2020 and is led by Professor Vincent Christoffels (UvA). Further involved is hDMT PI Roeland Merks, Professor of Mathematical Biology, from the Mathematical Institute of Leiden University.