A scalable and physiologically relevant system for human induced pluripotent stem cell expansion and differentiation

Human induced pluripotent stem cells (iPSCs) and their derivatives are needed in large numbers for various biomedical applications. However, scalable and cost-effective manufacturing of high quality iPSCs and their derivatives remains a challenge. In vivo, cells reside in a 3D microenvironment that has plenty of cell-cell and cell-ECM (extracellular matrix) interactions, sufficient supply of nutrients and oxygen, and minimal hydrodynamic stresses. The current iPSC culturing methods, however, provide highly-stressed culturing microenvironments, leading to low culture efficiency. For instance, we and others showed iPSCs typically expanded 4-fold/4 days to yield ~2.0x10^6 cells/mL with current 3D suspension culturing. These cells occupy ~0.4% of the bioreactor volume. To our best knowledge, the largest culture volume demonstrated to date for iPSCs is less than 10 liters. There is a critical need to develop new culture technologies to achieve the iPSCs’ potential. Please click Additional Files below to see the full abstract