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  4. Extracellular vesicles released by transforming growth factor-beta 1-preconditional mesenchymal stem cells promote recovery in mice with spinal cord injury

Extracellular vesicles released by transforming growth factor-beta 1-preconditional mesenchymal stem cells promote recovery in mice with spinal cord injury

Bioactive Materials, 2024 · DOI: https://doi.org/10.1016/j.bioactmat.2024.01.013 · Published: January 25, 2024

Spinal Cord InjuryRegenerative MedicineGenetics

Simple Explanation

Spinal cord injury (SCI) leads to inflammation and nerve cell damage. The study explores using extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) to treat SCI in mice. MSCs were pre-treated with TGF-β1 to enhance EV production. These EVs, called T-EVs, were injected into SCI mice and compared to EVs from untreated MSCs (C-EVs). The results showed T-EVs improved recovery by reducing inflammation, protecting nerve cells, and promoting the growth of new nerve tissue. The T-EVs may activate endogenous neural stem cells (eNSCs) via the mTORC2/Rictor pathway.

Study Duration
8 weeks
Participants
C57BL/6J mice
Evidence Level
Not specified

Key Findings

  • 1
    T-EVs enhanced the proliferation and antiapoptotic ability of NSCs in vitro and increased the shift from M1 to M2 polarization of reactive microglia, alleviating neuroinflammation.
  • 2
    T-EVs increased the number of eNSCs around the injury epicenter, promoted neurite outgrowth, increased axonal regrowth and remyelination, and facilitated locomotor recovery.
  • 3
    In Rictor−/−SCI mice, T-EVs failed to sufficiently increase eNSC activation and improve neurogenesis, suggesting T-EVs activate eNSCs via the mTORC2/Rictor pathway.

Research Summary

This study investigates the therapeutic potential of extracellular vesicles (EVs) derived from TGF-β1-pretreated mesenchymal stem cells (T-EVs) in treating spinal cord injury (SCI) in mice. The findings demonstrate that T-EVs promote functional recovery by reducing inflammation, protecting residual cells, enhancing endogenous neural stem cell (eNSC) activation, and promoting neuronal regeneration. The study suggests that T-EVs may exert their therapeutic effects by activating eNSCs via the mTORC2/Rictor signaling pathway, offering a potential target for optimizing SCI treatment.

Practical Implications

Therapeutic Potential

TGF-β1-pretreated MSC-derived EVs offer a promising therapeutic approach for treating SCI.

Mechanism of Action

The mTORC2/Rictor pathway is identified as a potential target for optimizing the function of eNSCs in SCI treatment.

EV Production

TGF-β1 can be used to enhance the production of MSC-derived EVs with improved therapeutic efficacy.

Study Limitations

  • 1
    The detailed mechanism, including the difference between C-EVs and T-EVs, should be identified to explain why T-EVs have superior efficacy in SCI repair.
  • 2
    Further investigations are needed to explore the molecular mechanisms of T-EVs and the effects of other factors on improving recovery after SCI.
  • 3
    Not specified

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