Cerebrospinal ﬂuid-derived extracellular vesicles after spinal cord injury promote vascular regeneration via PI3K/AKT signaling pathway

Journal of Orthopaedic Translation, 2023 · DOI: https://doi.org/10.1016/j.jot.2023.02.001 · Published: February 6, 2023

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This study explores the potential of cerebrospinal fluid-derived extracellular vesicles (CSF-EVs) in promoting recovery after spinal cord injury (SCI). CSF-EVs are isolated from pigs with SCI and combined with hydrogel, then applied to the injured spinal cord of mice. The research investigates whether these CSF-EVs can improve neurofunctional recovery, focusing on angiogenesis (blood vessel formation) and the activation of the PI3K/AKT signaling pathway, which is important for cell growth and survival. The findings suggest that CSF-EVs, particularly those from pigs with SCI, can enhance vascular regeneration and improve motor function recovery in mice with SCI by activating the PI3K/AKT pathway, potentially offering a new therapeutic approach for acute SCI.

Study Duration

Not specified

Participants

Female Bama miniature pigs (8 weeks old) and Female C57BL/6 mice (8 weeks old)

Evidence Level

Not specified

Key Findings

1
CSF-EVs, especially those derived from pigs with SCI (SCI-EVs), promote vascular regeneration more effectively than those from pigs without SCI (Sham-EVs).
2
SCI-EVs significantly enhance motor and sensory function in mice with SCI, indicating improved neurological recovery.
3
SCI-EVs activate the PI3K/AKT signaling pathway to promote angiogenesis, and inhibiting this pathway attenuates the pro-angiogenic effect of SCI-EVs.

Research Summary

This study investigates the therapeutic potential of cerebrospinal fluid-derived extracellular vesicles (CSF-EVs) for spinal cord injury (SCI). The researchers isolated CSF-EVs from pigs with SCI and applied them to mice with SCI to assess their impact on neurofunctional recovery. The key findings indicate that CSF-EVs, particularly those derived from SCI pigs, promote vascular regeneration and improve motor function recovery in mice with SCI. This effect is mediated by the activation of the PI3K/AKT signaling pathway. The study concludes that CSF-EVs offer a potential novel therapeutic option for acute SCI by enhancing vascular regeneration through the PI3K/AKT pathway, leading to improved motor function recovery.

Practical Implications

Potential Therapeutic Approach

CSF-derived exosomes could be developed into a therapeutic approach for treating spinal cord injuries due to their promotion of vascular regeneration and neurological function.

Drug Delivery

EVs can be used as drug carriers to simultaneously load multiple factors to promote angiogenesis

Targeted Therapy

Further research into the specific molecular composition of CSF-EVs could allow for the creation of targeted therapies.

Study Limitations

1
The study did not determine whether CSF-EVs influence vascular permeability or local inflammatory responses.
2
The factors that mediate the role of EVs in increasing angiogenesis were not identified due to the lack of high-throughput sequencing of CSF-EVs.
3
The alteration of CSF-EVs content in mice or patients have not been explored.

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