Human Nasal Olfactory Stem Cell-Derived Extracellular Vesicles Improve the Repair of Rat Nerves

Abstract

Background: Damage to the peripheral nerve significantly impairs quality and way of life. Despite the slow self-regeneration of the peripheral nervous system and advances in surgery, complete recovery after nerve injury remains elusive especially when there is loss of substance. Human olfactory ecto-mesenchymal stem cells (OEMSC) have potential for the treatment of peripheral nerve injury through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EV). The current research investigates the therapeutic effects of a venous bridge, filled with freshly purified or cryoconserved OEMSC-derived EVs after a peroneal nerve loss of substance. Methods: A 7 mm defect of peroneal nerve was bridged with a vein into which freshly purified or cryoconserved OEMSC-derived EVs were injected or not. These groups were compared with unoperated rats (Control) and autografted rats with the nerve sutured in inverted position (Gold Standard). Three months after surgery, nerve repair was analyzed by measuring locomotor function, muscle mechanical properties, muscle mass, axon number, and myelination. Results: We observed that OEMSC-derived EVs significantly (i) increased locomotor recovery, (ii) partially maintained the contractile phenotype of the target muscle, and (iii) augmented the number of growing axons. Freshly purified EVs exerted a better recovery than the Gold Standard. Conclusion: These results demonstrate that EVs display a positive effect on peripheral nerve regeneration, similarly to what has been observed with OEMSCs, the cells from which they originate. They represent an alternative to cellular therapies for peripheral nerve repair.

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