Extracellular Vesicles Derived From Olfactory Ensheathing Cells Promote Peripheral Nerve Regeneration in Rats.

Bing Xia,Jinghui Huang,Zhuojing Luo,Shengyou Li,Liangliang Huang,Yujie Yang,Teng Ma,Laihe Zhao,Jianbo Gao

doi:10.3389/fncel.2019.00548

Bing Xia, Jinghui Huang + Show 7 more

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https://doi.org/10.3389/fncel.2019.00548

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Abstract

Accumulating evidence showed that extracellular vesicles (EVs) and their cargoes are important information mediators in the nervous system and have been proposed to play an important role in regulating regeneration. Moreover, many studies reported that olfactory ensheathing cells (OECs) conditioned medium is capable of promoting nerve regeneration and functional recovery. However, the role of EVs derived from OECs in axonal regeneration has not been clear. Thereby, the present study was designed to firstly isolate EVs from OECs culture supernatants, and then investigated their role in enhancing axonal regeneration after sciatic nerve injury. In vitro studies showed that OECs-EVs promoted axonal growth of dorsal root ganglion (DRG), which is dose-dependent and relies on their integrity. In vivo studies further demonstrated that nerve conduit containing OECs-EVs significantly enhanced axonal regeneration, myelination of regenerated axons and neurologically functional recovery in rats with sciatic nerve injury. In conclusion, our results, for the first time, demonstrated that OECs-EVs are capable of promoting nerve regeneration and functional recovery after peripheral nerve injuries in rats.

Highlights

Olfactory ensheathing cells (OECs) are specialized glial cells located in the olfactory system which guide growing axons of olfactory receptor neurons of the olfactory mucosa through the cribriform plate and travel to the olfactory bulb, thereby allowing axons to travel from the peripheral nervous system (PNS) to the central nervous system (CNS; Radtke and Kocsis, 2014)
OECs were harvested and purified from SD rat olfactory bulbs and the cell purity was determined by the average ratio of smooth muscle α-actin (SMA) and p75NTR double-positive cell number to DAPI
Western blotting confirmed that the isolated preparations carried the characteristic extracellular vesicles (EVs) markers Alix, TSG101 and CD63, while calnexin, an integral protein were not detected in EVs (Figure 1E)

Summary

Introduction

Olfactory ensheathing cells (OECs) are specialized glial cells located in the olfactory system which guide growing axons of olfactory receptor neurons of the olfactory mucosa through the cribriform plate and travel to the olfactory bulb, thereby allowing axons to travel from the peripheral nervous system (PNS) to the central nervous system (CNS; Radtke and Kocsis, 2014). Neurogenesis allows for the replacement of olfactory receptor neurons, which is ongoing throughout the whole life in mammals (Mackay-Sim and Kittel, 1991). Many previous studies have shown that OECs are capable of enhancing nerve regeneration in both PNS and CNS (Verdú et al, 1999; Franssen et al, 2007; Radtke et al, 2009). It has been reported that long-term cultured OECs failed to support regeneration and neural repair (Verdú et al, 1999; Radtke et al, 2010), which (Verdú et al, 1999) might be attributable to the decreased viability of the transplanted

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