Construction of Mouse‐Embryonic‐Cell‐Derived 3D Pacemaker Tissues by Layer‐by‐Layer Nanofilm Coating

Abstract For the treatment of cardiac arrhythmia, electronic pacemakers are often employed. However, they have issues such as bio‐incompatibility and battery limitations. Recently, the use of cells expressing hyperpolarization‐activated cyclic nucleotide‐gated 4 (HCN4) channels for use as pacemaker cells instead of electronic pacemakers has attracted increasing attention. However, the cell transplantation treatment was not sufficiently effective because of the low engraftment rate of the transplanted cells and the risk of inflammatory reactions. Here, in order to overcome these issues, we constructed 3D‐pacemaker tissues composed of mouse‐embryonic‐cell‐derived cardiomyocytes (mESC‐CMs) in which the HCN4 gene had been introduced by the cell accumulation technique. The obtained tissues beat faster than control tissues and beats per minute (BPM) increased clearly with tissue thickness. This is the first report suggesting the relation between BPM and tissue thickness. Moreover, the pacemaker tissue could control the beating of the patched tissue.