iPSC-derived Motor Neuron Generation Service

Motor neurons are a specialized type of neuron in the central nervous system that transmits signals from the brain and spinal cord to skeletal muscles, controlling voluntary movement. Motor neuron degeneration is a hallmark of diseases like amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).

Motor neurons can be generated from induced pluripotent stem cells (iPSCs) using specialized differentiation protocols. iPSCs are stem cells that have been reprogrammed from adult somatic cells, such as skin or blood cells, back into a pluripotent state. These iPSCs can then be directed to differentiate into motor neuron progenitors and eventually develop into mature motor neurons.

Key Advantages of iPSC-derived Motor Neurons

• Renewable source avoiding the use of primary fetal or animal neurons
• Acquire homogeneous populations of motor neurons
• Generate patient-specific lines to model diseases
• Study motor neuron development, function, and vulnerability
• Screen for neuroprotective drugs

Applications of iPSC-derived Motor Neurons

• Modeling motor neuron diseases like ALS and SMA

Study patient motor neurons harboring ALS mutations (SOD1, TDP-43, etc.) or SMN1 deficiency.

• Investigating non-cell autonomous disease mechanisms

Co-culture motor neurons with other neural cells like astrocytes to examine non-cell autonomous toxicity.

• Testing potential neuroprotective and regenerative therapies

Screen drugs and gene therapies that promote motor neuron survival and axon regeneration.

Common Techniques Utilize iPSC-derived Motor Neurons

• Co-culture systems

Co-cultured with astrocytes, microglia, and oligodendrocytes, to study and characterize interactions between motor neurons and non-neuronal cells, in order to better replicate the disease microenvironment found in vivo.

• Survival and degeneration assays

Measure motor neuron viability, apoptosis markers, and mitochondrial defects under disease conditions.

• Neuromuscular junction formation assays

Co-culture with muscle cells to assess functional neuromuscular junction formation.

• Electrophysiology and calcium imaging

Examine motor neuron firing properties and calcium handling using patch clamp, MEA, and fluorescent dyes.

• Transcriptomics and motor neuron signature profiling

RNA-sequencing to characterize motor neuron maturation and disease-related gene expression changes.

Motor Neuron Diseases

• Amyotrophic lateral sclerosis (ALS)

Mutations in genes like SOD1, TDP-43, FUS, and C9orf72 cause motor neuron death in ALS patients.

• Spinal Muscular Atrophy (SMA)

Genetic deficiency in the SMN1 gene impairs motor neuron survival and function in SMA.

• Spinal Muscular Atrophy With Respiratory Distress (SMARD)

Mutations in the IGHMBP2 gene lead to infantile motor neuron degeneration.

• Hereditary Spastic Paraplegia (HSP)

Genetic deficiency of the SPG4 gene in motor neurons results in a significant increase in axonal swellings in HSP.

Reference

1. Bianchi, Fabio et al. "Rapid and efficient differentiation of functional motor neurons from human hiPSC for neural injury modelling." Stem Cell Res. 2018;32:126-134. Distributed under Open Access license CC BY 4.0. The original image was modified.