Exosomes and Their MicroRNA Cargo: New Players in Peripheral Nerve Regeneration

Abstract

Peripheral nerve injury is a major clinical problem and often results in a poor functional recovery. Despite obvious clinical need, treatment strategies have been largely suboptimal. In the nervous system, exosomes, which are nanosized extracellular vesicles, play a critical role in mediating intercellular communication. More specifically, microRNA carried by exosomes are involved in various key processes such as nerve and vascular regeneration, and exosomes originating from Schwann cells, macrophages, and mesenchymal stem cells can promote peripheral nerve regeneration. In this review, the current knowledge of exosomes' and their miRNA cargo's role in peripheral nerve regeneration are summarized. The possible future roles of exosomes in therapy and the potential for microRNA-containing exosomes to treat peripheral nerve injuries are also discussed.

Keywords: exosomes; microRNA; nerve regeneration; peripheral nerve injury.

Figure 1

Schematic representation of how miRNA containing exosomes play an important role in cell to cell communication. Exosomes packed with information such as microRNAs are released from source cells and taken up by target cells, thereby facilitating multilevel transfers of information and playing an important role in the development and physiology of neural systems.

Figure 2

Schematic representation of possible routes of exosomal miRNA to improve peripheral nerve regeneration. During peripheral nerve injury, a complex sequence of events is triggered inside the neuron’s cell body and in neighboring cells. Schwann cells, inflammation, trophic factors and angiogenesis are all involved in the nerve regeneration process. Encapsulate miRNAs in the exosomes play an important role in the peripheral nerve regeneration. Schwann cell exosomes which encapsulated miRNA340 and miR221 could be used to enhance nerve regeneration. Evidence has shown that miRNA containing exosomes from differentiated MSC can also directly enhance axonal regeneration, or indirectly promote recovery by regulating the inflammation response to promote nerve repair. Macrophages also secrete miRNA containing exosomes that can improve Schwann cell migration and proliferation, axon regeneration and angiogenesis to enhance peripheral nerve regeneration. Abbreviation: MSCs, Mesenchymal stem cells. Exo, exosomes.