Modeling Axonal Degeneration Using Motor Nerve Organoids

Abstract

Degeneration of axons is characteristic of many devastating diseases including amyotrophic lateral sclerosis (ALS). However, lack of an in vitro neuronal culture system that mimics damages on nerves and axonal tracts hampered development of effective treatments. Here, we describe a method to model degeneration of motor neuron axons using motor nerve organoids that are formed with human induced pluripotent stem cells. In this protocol, motor neuron axon degeneration can be rapidly induced with chemical damages. Neuroprotective effects of compounds can be examined using the degenerated axons. This motor neuron axon bundle degeneration model should facilitate future screening for drugs against diseases affecting axon fascicles.

Keywords: Axonal degeneration; Induced pluripotent stem (iPS) cell; Microfluidic device; Motor neuron; Neurodegenerative disease; Organ-on-a-chip; Organoid.