Exosomes as a Promising Therapeutic Strategy for Peripheral Nerve Injury

Abstract

Peripheral nerve injury has a high incidence and often leads to severe losses of sensory and motor functions in the afflicted limb. Autologous nerve grafts are widely accepted as the gold standard for peripheral nerve repair, but the presence of inherent drawbacks dramatically reduces their usability. Numerous tissue engineering nerve grafts are developed as alternatives to autologous nerve grafts, and a variety of cells and neurotrophic factors are introduced into these grafts for improvement. However, they are still difficult to obtain satisfactory clinical results. Peripheral nerve regeneration following injury remains a significant challenge for researchers and clinicians. Exosomes are extracellular membranous nanovesicles that are secreted by most cells. As the key players of intercellular communication, exosomes play a fundamental role in the physiological and pathological processes of the nervous system. Accumulating evidence has suggested that exosomes can exert neurotherapeutic effects via mediating axonal regrowth, Schwann cell activation, vascular regeneration, and inflammatory regulation. Exosomes are emerging as a promising approach for treating peripheral nerve injury. Furthermore, they also provide possibilities for enhancing the repairing capacity of various nerve grafts. This review primarily highlights the regenerative effects of exosomes on peripheral nerve injury. The exosomes from distinct sources reported so far in the literature are summarized to understand their roles in the process of nerve repair. Moreover, the challenges that must be addressed in their clinical transformation are outlined as well. This review also provides further insight into the potential application of exosomes for peripheral nerve repair.

Keywords: Exosome; Schwann cell; axonal regrowth; inflammation; nerve regeneration; peripheral nerve injury; vascular regeneration..

Fig. (1)

The biogenesis, secretion, and structure of exosomes. The process starts with the inward budding of the plasma membrane and forms early endosomes. Subsequently, as endosomes mature, intraluminal vesicles (ILVs) are generated by further invagination of the late endosome membrane, resulting in the formation of multivesicular bodies (MVBs). Finally, MVBs may fuse with lysosomes for degradation. Alternatively, MVBs may fuse with the plasma membrane to release ILVs into extracellular space as exosomes. (A higher resolution / colour version of this figure is available in the electronic copy of the article).

Fig. (2)

The effects of exosomes on peripheral nerve regeneration. Exosomes can exert therapeutic effects via mediating axonal regrowth, Schwann cell activation, vascular regeneration, and inflammatory regulation, which contribute to providing a favorable microenvironment for peripheral nerve regeneration. (A higher resolution / colour version of this figure is available in the electronic copy of the article).