Human umbilical cord mesenchymal stem cells-derived extracellular vesicles facilitate the repair of spinal cord injury via the miR-29b-3p/PTEN/Akt/mTOR axis

Xiao Xiao,Weiwei Li,Zhenchao Xu,Hongru Ye,Dingchao Rong,Yunqi Wu,Zhen Zhang,Yilu Zhang,Xiyang Wang,Liqiong Xie

doi:10.1038/s41420-021-00572-3

Xiao Xiao, Weiwei Li + Show 8 more

Open Access

https://doi.org/10.1038/s41420-021-00572-3

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Abstract

Spinal cord injury (SCI) is a salient traumatic disease that often leads to permanent disability, and motor and sensory impairments. Human umbilical cord mesenchymal stem cells (HucMSCs) have a wide application prospect in the treatment of SCI. This study explored the repair effect of HucMSCs-derived extracellular vesicles (HucMSCs-EVs) on SCI. HucMSCs and HucMSCs-EVs were cultured and identified. The rat model of SCI was established, and SCI rats were treated with HucMSCs-EVs. The motor function of SCI rats and morphology of spinal cord tissues were evaluated. Levels of NeuN, GFAP, and NF200 in spinal cord tissues were detected and cell apoptosis was measured. SCI rats were treated with EVs extracted from miR-29b-3p inhibitor-transfected HucMSCs. The downstream gene and pathway of miR-29b-3p were examined. HucMSCs-EVs-treated rats showed obvious motor function recovery and reduced necrosis, nuclear pyknosis, and cavity. HucMSCs-EVs alleviated spinal cord neuronal injury. miR-29b-3p was poorly expressed in SCI tissues, but highly expressed in EVs and SCI rats treated with EVs. miR-29b-3p targeted PTEN. Inhibition of miR-29b-3p or overexpression of PTEN reversed the repair effect of EVs on SCI. EVs activated the AKT/mTOR pathway via the miR-29b-3p/PTEN. In conclusion, HucMSCs-EVs reduced pathological changes, improved motor function, and promoted nerve function repair in SCI rats via the miR-29b-3p/PTEN/Akt/mTOR axis.

Highlights

Spinal cord injury (SCI) is a perplexing traumatic disease that often leads to permanent disability, as well as motor and sensory impairments [1]
Human umbilical cord mesenchymal stem cells (HucMSCs) showed favorable osteogenic, adipogenic, and chondrogenic differentiation abilities (Fig. 1B). These results demonstrated that HucMSCs were isolated successfully
The results of nanoparticle tracking analyzer (NTA) showed that the particles presented multimodal distribution, and most of the particles were in the range of Extracellular vesicles (EVs) diameter (30–150 nm) (Fig. 1D)

Summary

Introduction

Spinal cord injury (SCI) is a perplexing traumatic disease that often leads to permanent disability, as well as motor and sensory impairments [1]. Statistics show that about 2.5 million patients are suffering from SCI in the world, with approximately 130,000 newly diagnosed cases reported each year [2]. SCI ruins the life quality of patients physically and psychologically and brings heavy social and economic burdens to patients [3]. The major pathologic hallmarks associated with secondary damage of SCI include inflammation, oxidative stress, necrosis, and neuronal apoptosis [4]. About 45% of SCI patients suffer severe neurological loss, and complete or incomplete tetraplegia or even respiratory compromise can be seen in some cases [5]. The treatment approaches for SCI patients mainly include pharmacological agents, surgical treatment, and cell therapy [6, 7]

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