Exosomes derived from olfactory ensheathing cells provided neuroprotection for spinal cord injury by switching the phenotype of macrophages/microglia

Bioengineering and Translational Medicine - Tập 7 Số 2 - 2022
Hong Fan1,2, Zhe Chen2, Hai‐Bin Tang3, Lequn Shan2, Ziyi Chen4, Sheng Wang2, Dageng Huang2, Shichang Liu2, Xun Chen5, Hao Yang2, Dingjun Hao2
1Department of Neurology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
2Department of Spine Surgery, Shaanxi Spine Medicine Research Center, Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, China
3Department of Laboratory Medicine, Xi’an Central Hospital, Xi’an Jiaotong University, Xi’an, China
4Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
5Department of Bone Microsurgery, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, China

Tóm tắt

AbstractTransplantation of olfactory ensheathing cells (OECs) has been demonstrated to be beneficial for spinal cord injury (SCI) by modulating neuroinflammation, supporting neuronal survival and promoting angiogenesis. Besides OECs, the conditioned medium (CM) from OECs has also been proved to have therapeutic effects for SCI, indicating that the bioactive substances secreted by OECs are essential for its protective effects. Nevertheless, there is still little information regarding the underlying mechanisms. Considering that exosomes are crucial for intercellular communication and could be secreted by different types of cells, we speculated that the therapeutic potential of OECs for SCI might be partially based on their exosomes. To examine whether OECs could secret exosomes, we isolated exosomes by polyethylene glycol‐based method, and identified them by electron microscopy study, nanoparticle tracking analysis (NTA) and western blotting. In view of phagocytic ability of microglia and its distinct roles in microenvironment regulation after SCI, we then focused the effects of OECs‐derived exosomes (OECs‐Exo) on microglial phenotypic regulation. We found that the extracted OECs‐Exo could be engulfed by microglia and partially reverse the LPS‐induced pro‐inflammatory polarization through inhibiting NF‐κB and c‐Jun signaling pathways in vitro. Furthermore, OECs‐Exo were found to inhibit the polarization of pro‐inflammatory macrophages/microglia while increased the numbers of anti‐inflammatory cells after SCI. Considering that the neuronal injury is closely related to the activation state of macrophages/microglia, co‐culture of microglia and neurons were performed. Neuronal death induced by LPS‐treated microglia could be significantly alleviated when microglia treated by LPS plus OECs‐Exo in vitro. After SCI, NeuN‐immunostaining and axonal tract‐tracing were performed to assess neuronal survival and axon preservation. Our data showed that the OECs‐Exo promoted the neuronal survival and axon preservation, and facilitated functional recovery after SCI. Our findings provide a promising therapeutic strategy for SCI based on exosome‐immunomodulation.

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Bioengineering and Translational Medicine

Tập 7 Số 2

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