Enhanced development of human pluripotent stem cell-derived cerebral organoids via an electrical stimulation bioreactor

•ES of human COs promotes proliferation of neural progenitor cells.•ES increases neurogenesis, function and network formation in human COs.•ES improves CO cortical plate organization into upper and deep layers. Human brain-like 3D cultures or brain organoids are promising models for expanding our knowledge of brain development and the mechanisms that contribute to neurological disorders. Moreover, it may address the hardware bottleneck for the fast-growing field of artificial intelligence and the development of brain-machine interfaces. Current methods for developing brain organoids are limited mainly due to insufficient differentiation and inaccurate structural organization. Here, a novel engineering approach is proposed to accelerates the development of human cerebral organoids by electrical stimulation via an electrical bioreactor. This approach not only promotes proliferation and neurogenesis but also improves function, network formation, and organization of the cortical plate into upper and deep layers in which PI3K/Akt pathway at least partially participates. These results demonstrate the impact of electrical stimulation on generation of more mature and the functional cerebral organoids and may provide new insights into the hardware of its applications.