Generation of a Motor Nerve Organoid with Human Stem Cell-Derived Neurons

During development, axons spontaneously assemble into a fascicle to form nerves and tracts in the nervous system as they extend within a spatially constrained path. However, understanding of the axonal fascicle has been hampered by lack of an in vitro model system. Here, we report generation of a nerve organoid composed of a robust fascicle of axons extended from a spheroid of human stem cell-derived motor neurons within our custom-designed microdevice. The device is equipped with a narrow channel providing a microenvironment that facilitates the growing axons to spontaneously assemble into a unidirectional fascicle. The fascicle was specifically made with axons. We found that it was electrically active and elastic and could serve as a model to evaluate degeneration of axons in vitro. This nerve organoid model should facilitate future studies on the development of the axonal fascicle and drug screening for diseases affecting axon fascicles. In this article, Ikeuchi and colleagues show that axons of stem cell-derived motor neurons spontaneously assembled into a unidirectional fascicle within a microchannel. The axon fascicles were electrically active and elastic and can model degeneration of axons in vitro. This model could facilitate studies on the development of the axon fascicles and drug screening for diseases affecting axon fascicles.