Small extracellular vesicles derived from mesenchymal stem cell facilitate functional recovery in spinal cord injury by activating neural stem cells via the ERK1/2 pathway

Xinyuan Hu; Xinyuan Hu; Zhong Liu; Xinru Zhou; Xinru Zhou; Qian Jin; Wenrong Xu; Xiao Zhai; Qiang Fu; Hui Qian; Hui Qian

doi:10.3389/fncel.2022.954597

Frontiers in Cellular Neuroscience (Aug 2022)

Small extracellular vesicles derived from mesenchymal stem cell facilitate functional recovery in spinal cord injury by activating neural stem cells via the ERK1/2 pathway

Xinyuan Hu,
Xinyuan Hu,
Zhong Liu,
Xinru Zhou,
Xinru Zhou,
Qian Jin,
Wenrong Xu,
Xiao Zhai,
Qiang Fu,
Hui Qian,
Hui Qian

Affiliations

Xinyuan Hu: Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China
Xinyuan Hu: Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao, China
Zhong Liu: Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xinru Zhou: Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China
Xinru Zhou: Department of Laboratory Diagnostics, Changhai Hospital, Naval Medical University, Shanghai, China
Qian Jin: Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China
Wenrong Xu: Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China
Xiao Zhai: Department of Orthopedics, Changhai Hospital, Naval Medical University, Shanghai, China
Qiang Fu: Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Hui Qian: Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China
Hui Qian: NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology, Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, China

DOI: https://doi.org/10.3389/fncel.2022.954597
Journal volume & issue: Vol. 16

Abstract

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Spinal cord injury (SCI) causes severe neurological dysfunction leading to a devastating disease of the central nervous system that is associated with high rates of disability and mortality. Small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hucMSC-sEVs) have been explored as a promising strategy for treating SCI. In this study, we investigated the therapeutic effects of the intralesional administration of hucMSC-sEVs after SCI and determined the potential mechanisms of successful repair by hucMSC-sEVs. In vivo, we established the rat model of SCI. The Basso, Beattie, Bresnahan (BBB) scores showed that hucMSC-sEVs dramatically promoted the recovery of spinal cord function. The results of the hematoxylin–eosin (HE) staining, Enzyme-Linked Immunosorbent Assay (ELISA), and immunohistochemistry showed that hucMSC-sEVs inhibited inflammation and the activation of glia, and promoted neurogenesis. Furthermore, we studied the effect of hucMSC-sEVs on neural stem cells(NSCs) in vitro. We found that hucMSC-sEVs did not improve the migration ability of NSCs, but promoted NSCs to proliferate and differentiate via the ERK1/2 signaling pathway. Collectively, these findings suggested that hucMSC-sEVs promoted the functional recovery of SCI by activating neural stem cells via the ERK1/2 pathway and may provide a new perspective and therapeutic strategy for the clinical application of hucMSC-sEVs in SCI treatment.

Published in Frontiers in Cellular Neuroscience

ISSN: 1662-5102 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: http://www.frontiersin.org/cellular-neuroscience

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