Cell-matrix adhesions in cardiac progenitor cell mechanosensing and mechanoresponse
Cell-based cardiac regenerative therapies aim at restoring heart function and structure following cardiac disease, such as myocardial infarction. Human endogenous cardiomyocyte progenitor cells (CMPCs) are considered a valuable cell source since they are able to differentiate into cardiomyocytes and have shown to improve cardiac function when injected in the injured heart. To improve the effect of stem cell therapy, the injection of stem cells can be combined with a biomaterial, which can ameliorate cell retention, survival and differentiation. When injected in the injured myocardium, cells encounter a hostile environment, due to the altered mechanical properties of infarcted heart, and their mechanoresponse can dramatically influence the outcome of the treatment. In particular, the injected cells should be able to align with the local cardiomyocytes, in order to achieve a more homogeneous distribution of the electrical signal conduction and force generation, with an overall better therapeutic outcome.
The mechanism used by cells to sense and respond to biomechanical cues is called mechanotransduction, and is mainly regulated by cell-matrix adhesion proteins, i.e. integrins and integrin-linked proteins (e.g. vinculin, FAK, talin).
This PhD project is focused on studying cardiac progenitor cell (CMPC) response to mechanical stimuli, with a focus on the development and activation of their mechanosensing apparatus and the key signaling mechanisms that regulate CMPC mechanotransduction.