Dylan Mostert


Project description

The striated muscle of the heart (myocardium) is organized into anisotropic layers, consisting of beating cardiomyocytes (CMs) and structure supporting cardiac fibroblasts (cFBs). Upon injury, a lack of oxygen results not only in a massive loss of beating CMs but also in disruption of the highly organized architecture, impairing coordinated contraction, differentiation, matrix remodeling and mechanotransduction of resident and newly injected or recruited cardiac cells. Although many attempts have been made to restore the number of CMs after injury, there is little evidence of substantial long-term survival or engraftment of transplanted cells, suggesting the hostile fibrotic environment is opposing any attempt of cardiac regeneration.

In this project, we aim to gain fundamental knowledge on how we can use mechanobiological cues, inherent in the myocardium, to (re)engineer the tissue anisotropy that typifies healthy myocardial tissue. To do so, we use 2D and 3D in vitro models of the myocardial wall, consisting of cultures of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) and human epicardial derived cardiac fibroblasts (cFBs). To obtain insights on which mechanobiological cues drive anisotropic myocardial organization during the development of chicken embryos in vivo, we started a research collaboration with the Meinig School of Biomedical Engineering (Cornell University, USA) where Dylan currently works as a visiting postdoc under supervision of Prof. Dr. Jonathan T. Butcher.


Techniques: micro-contact printing, dynamic cell culture, 3D hydrogel culture, hPSC culture and cardiac differentiation, live-imaging.
Keywords: cardiovascular tissue engineering, cardiac organization, stem cells, mechanobiology, developmental biology.