Abstract

Exosomes, a kind of extracellular vesicle, are promising therapeutic agents for spinal cord injury (SCI). This article aimed to investigate effects of exosomes secreted from miRNA-29b-modified bone marrow mesenchymal stem cells (BMSCs) on SCI. Exosomes were extracted from BMSCs transfected with miRNA-29b or negative control (miR NC). SCI rats were injected intravenously with exosomes (control exosomes, miRNA-29b exosomes) and BMSCs (miR NC, miRNA-29b) through the tail vein. The expression of miRNA-29b in spinal cord tissues of SCI rats was detected by qRT-PCR. The hind limb motor function was evaluated by Basso Beattie Bresnahan (BBB) score. The histopathological damage and neuronal regeneration in spinal cord tissues was observed by HE staining and immunohistochemistry, respectively. The injection of miRNA-29b exosomes and miRNA-29b BMSCs both significantly increased the expression of miRNA-29b in spinal cord tissues of SCI rats (P<0.05). Compared with SCI rats, rats in the miRNA-29b exosomes and the miRNA-29b groups exhibited improved SCI, including increased BBB score, NF200 and GAP-43 positive neurons, as well as decreased contractile nerve cell numbers and GFAP positive neurons (all P<0.05). The relieving degree of SCI was significantly higher in the miRNA-29b exosomes group than in the miRNA-29b BMSCs group (P<0.05). Exosomes secreted from miRNA-29b-modified BMSCs were effective in the repair of SCI in rats.

Highlights

  • Spinal cord injury (SCI) is a serious central nervous system disease that leads to severe leg dysfunction and even lifelong paralysis [1]

  • The morphology of bone marrow mesenchymal stem cells (BMSCs) was consistent with the morphological characteristics of BMSCs [21]

  • After 72 h of transfection with miRNA-29b and miRNA-29b or negative control (miR NC), more than 95% of BMSCs showed positive expression of enhanced green fluorescent protein (EGFP) (Figure 1C and D)

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Summary

Introduction

Spinal cord injury (SCI) is a serious central nervous system disease that leads to severe leg dysfunction and even lifelong paralysis [1]. The transplantation of bone marrow mesenchymal stem cells (BMSCs) has been considered an effective therapeutic strategy for SCI, since it can inhibit inflammation and apoptosis, promote axonal regeneration and angiogenesis, reduce astrocyte scars and syringomyelia, and promote recovery of motor function [4]. Exosomes exert positive therapeutic effects on SCI through inhibiting neuronal apoptosis and inflammatory response [7]. Huang et al [9] found that the administration of mesenchymal stem cells (MSCs)-derived exosomes in SCI rats miRNA-29b exosomes relieved SCI significantly attenuates the lesion size, as well as cellular apoptosis and inflammation in the injured spinal cord. Wang et al [11] found that MSC-derived exosomes exert obvious neuroprotective effects on SCI by reducing SCI-induced A1 astrocytes and inhibiting inflammation. Exosomes are expected to be an alternative to stem cells in the treatment of SCI

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