Contributions of bone morphogenetic proteins in cardiac repair cells in three-dimensional in vitro models and angiogenesis

One of the main efforts in myocardial tissue engineering is towards designing cardiac tissues able to rescue the reduction in heart function once implanted at the site of myocardial infarction. To date, the efficiency of this approach in preclinical applications is limited in part by our incomplete understanding of the inflammatory environment known to be present at the site of myocardial infarct and by poor vascularization. It was recently reported that polarized macrophages known to be present at the site of myocardial infarction secrete bone morphogenetic proteins (BMPs)-2 and -4 causing changes in the expression of cardiac proteins in a 2D in vitro model. Here, these findings were extended towards cardiac tissues composed of human embryonic stem cell derived cardiomyocytes embedded in collagen gel. By preconditioning cardiac tissues with BMPs, constructs were obtained with enhanced expression of cardiac markers. Additionally, after BMP preconditioning, the resulting cardiac-tissues were able to sustain diffusion of the BMPs with the added benefit of supporting human umbilical vein endothelial cell tube formation. Here, a model is proposed of cardiac tissues preconditioned with BMPs that results in stimulation of cardiomyocyte function and diffusion of BMPs able to support angiogenesis. This platform represents a step towards the validation of more complex bioengineered constructs for in vivo applications.