Modeling ALS with motor neurons derived from human induced pluripotent stem cells

In this Review, a collaboration of leading experts in amyotrophic lateral sclerosis (ALS) research present the state of the field regarding the use patient-derived induced pluripotent stem cells to generate motor neurons in vitro. Motor neuron characterization, including transcriptomics, molecular markers, neuron function and electrophysiology, are discussed in the context of maturation and disease. Directing the differentiation of induced pluripotent stem cells into motor neurons has allowed investigators to develop new models of amyotrophic lateral sclerosis (ALS). However, techniques vary between laboratories and the cells do not appear to mature into fully functional adult motor neurons. Here we discuss common developmental principles of both lower and upper motor neuron development that have led to specific derivation techniques. We then suggest how these motor neurons may be matured further either through direct expression or administration of specific factors or coculture approaches with other tissues. Ultimately, through a greater understanding of motor neuron biology, it will be possible to establish more reliable models of ALS. These in turn will have a greater chance of validating new drugs that may be effective for the disease.