Disease modeling


The use of human iPS cells from cardiac patients in hDMT’s heart disease models offers unprecedented opportunities for mimicking genetic diseases in vitro, since the genome of the patient is captured in the derivative heart cells in culture. This allows one to determine whether the patients’ cells show any abnormal electrical or metabolic activity compared to heart cells of healthy people, and to study how patients with specific gene mutations that trigger an inherited heart disease, respond to different drugs.

Risk 

An important research question is how to differentiate iPS cells into heart muscle cells that are developmentally more mature. As many heart diseases take years to manifest in patients, there is a risk that they do not appear in the relatively immature heart cells that have been generated so far.

3D co-culture

More complex heart-on-chip disease models are needed when the dysfunction results from a complicated interaction of various cell types. One of the objectives in the Heart-on-Chip program is to mimic this interaction by realizing 3D co-culture of all cell types that make up the heart (including the fibroblasts that synthesize the extracellular matrix) and to get a deeper understanding of this interaction. This is made possible by hDMT’s expertise in stem cell biology, biomaterials, microfluidics, nanotechnology, mechanics, electronics,  single-cell technologies and metabolomics, combined with a number of advanced readout technologies.

To maintain heart tissue for a longer period of time it has to be continuously perfused by nutrients, which calls for the integration of the “heart-on-a-chip”  into a vessels-on-chip microfluidic device (creating an interface with the Vessels-on-Chip program). The resulting (low throughput) heart disease mimics can be used for drug target discovery and for ‘clinical trial on a chip’ testing.