Additive manufacturing enables production of de novo cardiomyocytes by controlling embryoid body aggregation

Abstract

Embryonic stem cells act as a valuable and promising resource in the field of regenerative cell-based therapies and in studying various developmental models. These derived cells can be induced in vitro to differentiate into numerous distinct cell lineages by the formation of Embryoid Bodies (EBs), in a process strongly conditioned by the geometrical characteristics of the EB. This artificial conditioning of cellular differentiation is performed using tools prioritizing geometrical definition but lacking versatility for the adaptation of the geometry to different conditions. Here we demonstrate the production of cardiomyocytes by using high definition direct writing technologies to influence EB aggregation from stem cells. We gauged the impact of this technology over the standard known methods in terms of size dispersion, cell packing density, cardiac tissue health, and the number of cardiomyocytes produced. The feasibility to create small variations of a geometry enabled optimizing EB formation for cardiogenesis and its threefold increase with respect to traditional techniques. This result highlights how the fast-paced improvement of geometrical control in additive manufacture might hold the key to unprecedented control of stem cell differentiation for regenerative medicine.