Limitations and Challenges in Modeling Diseases Involving Spinal Motor Neuron Degeneration in Vitro

The review discusses the limitations of current in vitro models for studying spinal motor neuron (MN) degeneration, focusing on the challenges of replicating mature MN characteristics and the complex interactions with other cell types. Current models primarily use immature neurons, which differ significantly from the mature MNs affected in diseases like ALS and sarcopenia. This immaturity limits the models' ability to accurately represent disease mechanisms. The review emphasizes the need for models that incorporate the interactions between MNs, glial cells, Schwann cells, and muscle cells to better mimic the in vivo environment and study neurodegenerative processes comprehensively.

• 1
  Current in vitro models of spinal motor neuron degeneration often rely on immature neurons, which do not fully represent the characteristics of mature neurons affected in diseases like ALS.
• 2
  The absence of crucial cell-cell interactions, particularly between MNs, glial cells, Schwann cells, and muscle cells, in existing models limits their ability to accurately mimic the complex in vivo environment.
• 3
  Developing reliable and translational in vitro platforms for studying spinal MN degeneration requires overcoming challenges related to MN maturation, co-culture complexity, and the faithful emulation of the in vivo environment.