Cells will be a major type of medicine. To achieve the full potential of cellular therapeutics, we must be able to cost-effectively and reproducibly manufacture cells at large scales and with high quality. Currently, robust and cost-effective culture of high-quality allogenic or autologous cells in large scales is still very challenging. Academia and industry are focusing on developing modular, disposable and closed bioreactors; automating the cell culture; integrating process analysis and control and artificial intelligence. This short article describes how the cell culture microenvironment impacts the cell culture outcome, and the critical need of creating a cell-friendly microenvironment during cell manufacturing.