4.7 Article

Exosomes derived from miR-26a-modified MSCs promote axonal regeneration via the PTEN/AKT/mTOR pathway following spinal cord injury

Journal

STEM CELL RESEARCH & THERAPY
Volume 12, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13287-021-02282-0

Keywords

Mesenchymal stem cells; Exosomes; Spinal cord injury; Axonal regeneration; miR-26a; PTEN axis

Funding

  1. National Key Research and Development Program of China [2017YFA0105400]
  2. National Natural Science Foundation of China [82072455, 81772349, 81772398, 81472122]
  3. Key Research and Development Program of Guangdong Province [20180236]
  4. Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR0201006]

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Exosomes derived from miR-26a-modified MSC can promote axonal regeneration, improve neurogenesis, and attenuate glial scarring through the PTEN/AKT/mTOR signaling cascades in spinal cord injury.
Background Exosomes derived from the bone marrow mesenchymal stem cell (MSC) have shown great potential in spinal cord injury (SCI) treatment. This research was designed to investigate the therapeutic effects of miR-26a-modified MSC-derived exosomes (Exos-26a) following SCI. Methods Bioinformatics and data mining were performed to explore the role of miR-26a in SCI. Exosomes were isolated from miR-26a-modified MSC culture medium by ultracentrifugation. A series of experiments, including assessment of Basso, Beattie and Bresnahan scale, histological evaluation, motor-evoked potential recording, diffusion tensor imaging, and western blotting, were performed to determine the therapeutic influence and the underlying molecular mechanisms of Exos-26a in SCI rats. Results Exos-26a was shown to promote axonal regeneration. Furthermore, we found that exosomes derived from miR-26a-modified MSC could improve neurogenesis and attenuate glial scarring through PTEN/AKT/mTOR signaling cascades. Conclusions Exosomes derived from miR-26a-modified MSC could activate the PTEN-AKT-mTOR pathway to promote axonal regeneration and neurogenesis and attenuate glia scarring in SCI and thus present great potential for SCI treatment.

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