The functional properties of nephronectin: An adhesion molecule for cardiac tissue engineering

Despite significant advances in preventive cardiovascular medicine and therapy for acute and chronic heart failure, cardiovascular diseases remain among the leading causes of death worldwide. In recent years cardiac tissue engineering has been established as a possible future treatment option for cardiac disease. However, the quality of engineered myocardial tissues remains poor. In tissue engineering it is important that the scaffold allows cells to attach, spread, maintain their differentiation status or differentiate into functional cells in order to exhibit their physiological function. Here, we have investigated the suitability of the natural cardiac extracellular matrix component nephronectin as an adhesive material for cardiac tissue engineering. Primary neonatal rat cardiomyocytes were seeded on collagen-, fibronectin- or nephronectin-coated glass coverslips and analyzed for cell adhesion, cellular metabolic activity, response to extracellular stimuli, cell-to-cell communication, differentiation and contractility. Our data demonstrate that most neonatal cardiomyocytes attached in an RGD domain-dependent manner within 18 h to nephronectin. The cells exhibited high metabolic activity, responded to growth factor stimuli and maintained their differentiation status. Moreover, nephronectin promoted sarcomere maturation and alignment, cell-to-cell communication and synchronous contractions. In conclusion, our findings demonstrate that nephronectin has excellent properties for cardiomyocyte adhesion and function and thus has the potential to improve current cardiac tissue engineering approaches.