Muscle-Derived Extracellular Vesicles Influence Motor Neuron Regeneration Accuracy

Extracellular vesicles are lipid bilayer-enclosed extracellular structures. Although the term extracellular vesicles is quite inclusive, it generally refers to exosomes (<200 nm), and microvesicles (~100-1000 nm). Such vesicles are resistant to degradation and can contain proteins, lipids, and nucleic acids. Although it was previously thought that the primary purpose of such vesicles was to rid cells of unwanted components, it is now becoming increasingly clear that they can function as intercellular messengers, sometimes operating over long distances. As such, there is now intense interest in extracellular vesicles in fields as diverse as immunology, cell biology, cancer, and more recently, neuroscience. The influence that such extracellular vesicles might exert on peripheral nerve regeneration is just beginning to be investigated. In the current studies we show that muscle-derived extracellular vesicles significantly influence the anatomical accuracy of motor neuron regeneration in the rat femoral nerve. These findings suggest a basic cellular mechanism by which target end-organs could guide their own reinnervation following nerve injury.