High‐Throughput Differentiation of Embryonic Stem Cells into Cardiomyocytes with a Microfabricated Magnetic Pattern and Cyclic Stimulation

Pluripotent stem cells are central tools to many regenerative medicine strategies due to their ability to differentiate toward the three embryonic germ layers. One challenge remains in providing control over their differentiation into specific lineages, such as cardiac commitment. Here, the possibility of directing cardiomyogenesis of embryonic stem cells using a microfabricated magnetic pattern is demonstrated. The stem cells are labeled with magnetic nanoparticles, aggregated into embryoid bodies (EBs) onto the pattern, and stimulated with a local magnetic force applied via the pattern. The EBs formed on this magnetic device experience the same differentiation profile as the ones created by the common hanging drop approach, while it allows high‐throughput production of hundreds of EBs. Further on/off cyclic magnetic force stimulation mediated by the same device is sufficient to enhance cardiomyogenesis in a way that almost all EBs develop spontaneous beating, confirmed by the overexpression of α‐actin and troponin proteins, and by the upregulation (twofold to fivefold) of genes involved in mesoderm differentiation (Nkx2.5, Gata4, and Gata6), and more specifically cardiac lineage (Tnnt2, Myh6, and Myl‐2). Beyond holding high application‐level potential, this work confirms that physical forces, and specifically on/off dynamic ones can be sufficient to govern cell function. Using a pattern of magnetic microtips and magnetically labeled embryonic stem cells, high‐throughput cell aggregation into embryoid bodies can be achieved. The magnetic pattern allows an on/off magneto‐mechanical stimulation of the stem cells, which impressively enhances their differentiation into cardiomyocytes when compared to a conventional hanging drop method, with over 90% of embryoid bodies developing spontaneous beating.