Engineering the niche to differentiate and deploy cardiovascular cells

Applications for stem cells have ranged from therapeutic interventions to more conventional screening and in vitro modeling, but significant limitations to each is due to the lack of maturity from decades old monolayer protocols. While those methods remain the 'gold standard,' newer three-dimensional methods, when combined with engineered niche, stand to significantly improve cell maturity and enable new applications. Here in three parts, we first discuss past methods, and where and why we believe those methods produced suboptimal myocytes. Second, we note how newer methods are moving the field into an era of cell mechanical, electrical, and biological maturity. Finally, we highlight how these improvements will solve issues of scale and engraftment to yield clinical success. It is our conclusion that only through a combination of diverse cell populations and engineered niche will we create an engineered heart tissue with the maturity and vasculature to integrate successfully into a host.