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Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Promote the Recovery of Spinal Cord Injury and Inhibit Ferroptosis by Inactivating IL-17 Pathway

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Abstract

Mesenchymal stem cell (MSC)-derived exosomes are considered as alternative to cell therapy in various diseases. This study aimed to understand the effect of bone marrow MSC-derived exosomes (BMMSC-exos) on spinal cord injury (SCI) and to unveil its regulatory mechanism on ferroptosis. Exosomes were isolated from BMMSCs and the uptake of BMMSCs-exos by PC12 cells was determined using PKH67 staining. The effect of BMMSC-exos on SCI in rats was studied by evaluating pathological changes of spinal cord tissues, inflammatory cytokines, and ferroptosis-related proteins. Transcriptome sequencing was used to discover the differential expressed genes (DEGs) between SCI rats and BMMSC-exos-treated rats followed by functional enrichment analyses. The effect of BMMSC-exos on ferroptosis and interleukin 17 (IL-17) pathway was evaluated in SCI rats and oxygen–glucose deprivation (OGD)-treated PC12 cells. The results showed that particles extracted from BMMSCs were exosomes that could be taken up by PC12 cells. BMMSC-exos treatment ameliorated injuries of spinal cord, suppressed the accumulation of Fe2+, malondialdehyde (MDA), and reactive oxygen species (ROS), with the elevated glutathione (GSH). Also, BMMSC-exos downregulated the expression of acyl-CoA synthetase long chain family member 4 (ACSL4) and upregulated glutathione peroxidase 4 (GPX4) and cysteine/glutamate antiporter xCT. A total of 110 DEGs were discovered and they were mainly enriched in IL-17 signaling pathway. Further in vitro and in vivo experiments showed that BMMSC-exos inactivated IL-17 pathway. BMMSC-exos promote the recovery of SCI and inhibit ferroptosis by inhibiting the IL-17 pathway, which provides BMMSC-exos as an alternative to the management of SCI.

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Data Availability

The RNAseq data had been uploaded to the Sequence Read Archive at https://www.ncbi.nlm.nih.gov/sra/PRJNA1081472 (Accession: PRJNA1081472).

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Funding

The work was supported by Science and Technology Project of Jiangxi Provincial Department of Education (No. GJJ2201435).

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Authors and Affiliations

  1. Department of Trauma Center, The First Affiliated Hospital of Gannan Medical University, No. 128, West Jinling Road, Ganzhou, 341000, China

    Wen Tang & Xiaozhong Zhou

  2. Department of Spine Surgery, The First Affiliated Hospital of Gannan Medical University, No. 128, West Jinling Road, Ganzhou, 341000, China

    Kai Zhao

  3. Center for Technology of Information and Network Management, Gannan Medical University, Ganzhou, 341000, China

    Xiaobo Li

  4. The First Clinical Medical College, Gannan Medical University, No. 128, West Jinling Road, Ganzhou, 341000, China

    Peigen Liao

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  1. Wen Tang
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  2. Kai Zhao
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  3. Xiaobo Li
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  4. Xiaozhong Zhou
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  5. Peigen Liao
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Contributions

Conceptualization, WT; methodology, WT and KZ; investigation, XBL, XZZ, and PGL; formal analysis, XBL, XZZ, and PGL; writing—original draft, WT, KZ, and XZZ; writing—review and editing, XBL and PGL. All authors took part in the experiment and approved the final version of the manuscript.

Corresponding author

Correspondence to Wen Tang.

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Ethics Approval and Consent to Participate

The animal experiments were approved by the Scientific Research Ethics Committee of The First Affiliated Hospital of Gannan Medical University (No. LLSC 2023 No.410) in accordance with the ARRIVE guidelines.

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Tang, W., Zhao, K., Li, X. et al. Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Promote the Recovery of Spinal Cord Injury and Inhibit Ferroptosis by Inactivating IL-17 Pathway. J Mol Neurosci 74, 33 (2024). https://doi.org/10.1007/s12031-024-02209-3

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