Mechanosensitivity of cardiomyocyte progenitor cells: the strain response in 2D and 3D environments

Cardiomyocytes progenitor cells (CMPCs) are a candidate cell source for cardiac regenerative therapy. To assess their full potential for cardiac regeneration, it is essential to know if and how CMPCs sense and respond to the... [ view full abstract ]

Cardiomyocytes progenitor cells (CMPCs) are a candidate cell source for cardiac regenerative therapy. To assess their full potential for cardiac regeneration, it is essential to know if and how CMPCs sense and respond to the three-dimensional (3D) environment and mechanical stimuli provided by the beating heart. Therefore, we study the response to uniaxial (cyclic) strain (10% with 0.5Hz) of undifferentiated and predifferentiated human CMPCs in a 2D environment, as well as how CMPCs respond to unidirectional constrained versus stress-free (unconstrained) 3D environments.

We observe that while undifferentiated CMPCs maintain their original orientation, upon early cardiomyogenic differentiation (predifferentiated) CMPCs exhibit a distinct re-orientation away from the applied strain (strain avoidance) during 48hrs of cyclic straining in a 2D environment. In 3D unidirectionally constrained hydrogels, undifferentiated CMPCs retain their cardiomyogenic stem cell profile. CMPCs cultured in 3D collagen/Matrigel hydrogels respond to static mechanical strains as expected by cell alignment.

Our results suggest that CMPCs respond to the presence of mechanical stimuli, proposing that CMPCs are indeed mechanosensitive, although in 2D environments mechanosensitivity of the CMPCs is dependent on their differentiation status. Our findings provide the first understanding of the ability of human CMPCs to sense mechanical stimuli, which is the initial step of mechanotransduction. Mechanotransduction is essential for optimal recruitment, migration, and mechanical integration of progenitor cells into the injured myocardium. Therefore, the presented results can contribute to enhance efficacy of current treatments of cardiac disease.