Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy

Cell Death & Disease, 2019 · DOI: 10.1038/s41419-019-1571-8 · Published: April 3, 2019

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injury (SCI) often leads to severe dysfunction of the limbs below the injured spinal segment, and more rostral (cervical injuries) may even be fatal. The treatment of SCI is rapidly evolving, and some experimental treatments have been examined in clinical trials. However, SCI remains largely irreversible and it is currently uncertain whether these therapies can safely improve prognosis. Neural stem cells (NSCs) have the ability to self-renew and produce neurons, oligodendrocytes, and astrocytes. In recent years, NSC transplantation has become a major focus in the study of SCI repair.

Study Duration

28 days

Participants

Adult male Sprague–Dawley rats (weighing 180−220 g)

Evidence Level

Level II: Experimental study

Key Findings

1
NSC-sEVs can significantly reduce the extent of SCI, improve functional recovery, and reduce neuronal apoptosis, microglia activation, and neuroinflammation in rats.
2
NSC-sEVs can regulate apoptosis and inflammatory processes by inducing autophagy. In brief, NSC-sEVs increased the expression of the autophagy marker proteins LC3B and beclin-1, and promoted autophagosome formation.
3
NSC-sEV treatment has the potential to reduce neuronal apoptosis, inhibit neuroinflammation, and promote functional recovery in SCI model rats at an early stage by promoting autophagy.

Research Summary

This study demonstrates for the ﬁrst time that NSC-derived sEVs can suppress neuronal apoptosis, microglia activation, and neuroinﬂammation, thereby promoting functional recovery in SCI model rats. These effects appear to depend on neuronal autophagy. Stem cell transplantation is considered a promising potential treatment for central nervous system diseases given the capacity of stem cells to differentiate into multiple cell types. Here, we conducted a series of experiments in vivo and in vitro to prove our hypothesis. First, we successfully extracted NSCs and isolated high concentrations of sEVs from the culture medium.

Practical Implications

Therapeutic Potential

NSC-sEVs show promise as a new biological treatment for SCI, offering a cell-free therapy option.

Mechanism of Action

The therapeutic effects of NSC-sEVs are linked to their ability to induce autophagy, providing insights into targeted therapies.

Overcoming Limitations

NSC-sEVs may circumvent the limitations of direct stem cell transplantation, such as low survival rates and tumorigenesis.

Study Limitations

1
Study was conducted on rats and may not directly translate to humans.
2
Long-term effects of NSC-sEV treatment were not evaluated.
3
The specific components of NSC-sEVs responsible for the observed effects were not fully identified.

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