Supersensitive Layer-by-Layer 3D Cardiac Tissues Fabricated on a Collagen Culture Vessel Using Human-Induced Pluripotent Stem Cells

Impact statement In recent years, development of three-dimensional (3D) cardiac tissue has been promoted in regenerative medicine and drug discovery. In this study, we fabricated a 3D cardiac tissue composed of induced pluripotent stem cell (iPSC)-derived cardiomyocytes by the layer-by-layer (LbL) and cell accumulation technique. Furthermore, we worked on improving the function of the 3D cardiac tissue using the collagen culture vessel. As a result, the contractile function and the sensitivity of detecting arrhythmia by drugs of 3D cardiac tissue were improved. The 3D cardiac tissue fabricated in this study is expected to promote regenerative medicine and drug discovery. Background:The fabrication of artificial cardiac tissue is an active area of research due to the shortage of donors for heart transplantation and for drug development. In our previous study, we fabricated vascularized three-dimensional (3D) cardiac tissue by layer-by-layer (LbL) and cell accumulation technique. However, it was not able to develop sufficient function because it was cultured on a hard plastic substrate. Experiment:Herein, we report the fabrication of high-performance 3D cardiac tissue by LbL and cell accumulation technique using a collagen culture vessel. Results:By using a collagen culture vessel, 3D cardiac tissue could be fabricated on a collagen culture vessel and this tissue showed high functionality due to improved interaction with the vessel. In the case of the plastic culture insert, 3D cardiac tissue was found to be peeled off, but this did not occur on the collagen culture vessel. In addition, the 3D cardiac tissue fabricated on a collagen culture vessel showed contraction that was 20 times larger than the tissue fabricated on a plastic culture insert. As a result of evaluation of cardiotoxicity using E-4031, the sensitivity of arrhythmia detection was increased by using collagen culture vessel. Conclusions:These results are expected to contribute to transplantation and drug discovery research as a 3D cardiac tissue model with a function similar to that of the living heart.