%0 Journal Article %T Creation of Scaffold-Free Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) Cell Sheets for Drug Screening and Regenerative Medicine %J - %D 2019 %R https://doi.org/10.1016/j.bpj.2018.11.1477 %X We describe a method to create a liquid surface to support self-assembly of cells, the curvature of which can be altered to produce cell sheets with different shapes. The assembly comprises a removable polydimethylsiloxane (PDMS) cell mold and a standard 96-well polystyrene (PS) microplate. The cell mold is inserted into each well of the plate to create an air-filled chamber between PDMS and PS. The sealed volume of air in the chamber provides mechanical support for the liquid inside the PDMS cell mold, allowing the bottom surface of the suspended liquid to be flat which we show to provide a supporting surface for self-assembly for cell cultures. Thereby, small scale scaffold-free cell sheets can be produced easily and repeatably. The size of the cell sheets can be varied from 1 to 3 mm depending on the size and shape of PDMS cell mold used. The thickness of the cell sheet ranges 0.06-0.1 mm day 1 after plating, representing 3-5 cell layers. The electrophysiology and contractility of the 3D culture layer containing commercially available human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) was investigated using the CellOPTIQ£¿ platform (Clyde Biosciences Ltd). Visible scaffold-free hiPS-CMs cell sheets formed after 24 hours of the cell seeding showed spontaneous rhythmic electrical and contractile activity; by comparison, traditional 2D hiPS-CMs cell culture required several days before comparable activity was evident. The 3D culture layer formed with the present method is thicker and more uniform than the traditional 2D monolayer cell culture. Scaffold-free 3D cell sheets made with the method therefore constitute pure tissue-like cell structures which are suitable for high throughput drug screening and have potential also for regenerative medicine %U https://www.cell.com/biophysj/fulltext/S0006-3495(18)32742-5