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 of autologous nerve grafts, and a variety of cells and neurotrophic factors were 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 repair 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 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, nerve regeneration, peripheral nerve injury, Schwann cell, axonal regrowth, inflammation, vascular regeneration.

Role of exosomes in the pathogenesis, diagnosis, and treatment of central nervous system diseases

“…The incidence of peripheral nerve injury (PNI) is very high, often leading to severe loss of sensory and motor function of the affected limb [ 127 ]. Autologous nerve transplantation is widely accepted as the gold standard for peripheral nerve repair, but its inherent defects greatly reduce their availability [ 128 ].…”

“…Regeneration after peripheral nerve injury is still a major challenge for researchers and clinicians. Increasing evidence show that exosomes can play a neurotherapeutic effect by mediating axon regeneration, Schwann cell activation, angiogenesis and inflammation regulation [ 127 ]. Besides, peripheral nerve injury may cause neuropathic pain.…”

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

“…In the peripheral nervous system, Schwann cells secrete exosomes that are internalized by neighboring axons, providing local axonal support and enhancing axonal regeneration after nerve damage [91]. Gomez-Molina et al provide evidence of two-way communication through exosomes from the brain to the rest of the body [92].…”

Role of the Peripheral Nervous System in PD Pathology, Diagnosis, and Treatment

“…It is thought that supplementing their natural function could enable targeted delivery of drug molecules (Mehryab et al, 2020). Multiple studies have confirmed that SC can secrete exosomes and that they have a powerful promotion effect on neuronal axon regeneration and improve neuronal viability (Hu et al, 2019;Yu et al, 2021). It was found that miRNA-21 expression was increased in secreted exosomes after SC upregulated the expression of c-jun and Sox2, which are key in promoting neurite growth by SC-derived exosomes (López-Leal et al, 2020).…”