Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons, but increasing evidence suggests that astrocytes and microglia also contribute to disease progression through mechanisms including neuroinflammation, altered cellular support and dysregulated cell-cell communication. Understanding these interactions is therefore critical for developing more physiologically relevant in vitro models and identifying new therapeutic targets.
The importance of neuron-glia interactions
Although motor neuron monocultures remain valuable tools, they do not fully capture the cellular complexity of the central nervous system. Astrocytes regulate neuronal homeostasis, metabolic support and synaptic activity, while microglia mediate immune surveillance and inflammatory responses.
Co-culture systems enable researchers to investigate how these cell populations influence motor neuron behaviour and contribute to disease-relevant phenotypes. Depending on experimental requirements, researchers may choose motor neuron-astrocyte, motor neuron-microglia or triculture models containing all three cell types.
The motor neuron, astrocyte and microglia triculture system supports the maintenance of all three cell types within a single culture, providing a more physiologically relevant platform for studying ALS biology.
Motor neuron, astrocyte and microglia triculture
Representative confocal image demonstrating the presence of motor neurons, astrocytes and microglia within the same culture system after 21 days in culture.
Glial cells modulate neuronal network activity
The addition of astrocytes and microglia directly influences motor neuron activity. In triculture experiments, the timing of glial cell addition altered burst strength, with earlier introduction of astrocytes and microglia resulting in earlier changes in neuronal network behaviour.
These findings highlight the importance of cellular context when modelling ALS and support the use of co-culture systems for investigating the functional consequences of neuron-glia interactions.
Astrocytes and microglia influence motor neuron activity
The presence of glial cells modifies spontaneous motor neuron burst activity, demonstrating the functional impact of neuron-glia interactions in human iPSC-derived triculture models. (A) Motor neuron monoculture on day 21 without accelerator supplement, (B) motor neurons with astrocytes and microglia added late, day 21. n=3., (C) motor neurons with astrocytes and microglia added early, day 21, n=3, (D) Glia
added late, (E) Glia added early.
Human iPSC-derived co-culture kits for neurodegeneration research
To support the study of neuron-glia interactions, Axol Bioscience has developed a range of human iPSC-derived co-culture kits comprising motor neurons, astrocytes and microglia in defined culture systems. The portfolio includes:
These kits provide researchers with a complete, standardized solution for studying neuron-glia interactions and investigating the contribution of glial cells to ALS and other neurodegenerative disorders.
Additional motor neurons, astrocytes and microglia can also be generated through our custom differentiation services.
