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

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.

The Role of Exosomes and Exosomal Noncoding RNAs From Different Cell Sources in Spinal Cord Injury

“…MSCs-Exos were separated and concentrated by ultracentrifugation and differential centrifugation in many studies (Huang et al, 2017 , 2020a ; Lankford et al, 2018 ; Wang et al, 2018 ; Guo et al, 2019 ; Ji et al, 2019 ; Kang et al, 2019 ; Li et al, 2019 ; Li C. et al, 2020 ; Li et al, 2021 ; Chen et al, 2021 ; Cheng et al, 2021 ; Han et al, 2021 ; Jia et al, 2021 ; Jiang and Zhang, 2021 ; Liu W. Z. et al, 2021 ; Liu et al, 2022 ; Nakazaki et al, 2021 ; Nie and Jiang, 2021 ; Noori et al, 2021 ; Sheng et al, 2021 ; Xiao et al, 2021 ; Xin et al, 2021 ; Zhang A. et al, 2021 ; Liang et al, 2022 ; Zhou et al, 2022 ) and by precipitation kits/polymer (PEG or others) in some studies (Li et al, 2018 ; Ren et al, 2019 ; Xu et al, 2019 ; Yu et al, 2019 ; Zhao et al, 2019 ; Fan et al, 2021 ; Jia et al, 2021a , b ; Kang and Guo, 2022 ). To achieve better specificity of MSCs-Exos separation, many researchers isolated MSCs-Exos using ultrafiltration-centrifugation combined with density-gradient ultracentrifugation (Liu et al, 2020 ; Shao et al, 2020 ; Chang et al, 2021 ; Luo et al, 2021 ; Huang et al, 2022 ).…”

The PI3K/AKT signalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities

“…203 PTEN is an inhibitor of the PI3K/AKT signalling pathway. Many miRNAs can affect the PI3K/AKT signalling pathway by regulating PTEN; these miRNAs include miR-29a-3p, 204 miR-29b-3p, 205 miR-212-3p, 206 miR-494 207 and miR-21. 208 Overexpression of these miRNAs after SCI inhibits PTEN expression through the PTEN/AKT signalling axis, thus decreasing apoptosis and inflammation; it also promotes the recovery of nerve function in SCI animals.…”

Photobiomodulation improves the therapeutic efficacy of mesenchymal stem cells in regenerative medicine

“…UCMSCs are MSCs derived from umbilical cord blood, capable of self-renewal and differentiation into multiple cell lineages. 44 The scientific use of human UCMSCs is regarded as clinically acceptable, 45 while ESC are faced with ethical hurdles. 46 One potential use of UCMSCs with PBM is repairing damaged tendons, which on their own regenerate poorly due to a dense extracellular matrix and low cellularity.…”