Bone marrow mesenchymal stem cells modulate miR-202-3p to suppress neuronal apoptosis following spinal cord injury through autophagy activation via the AMPK, MAPK, and PI3K/AKT/mTOR signaling pathway

Scientific Reports, 2024 · DOI: https://doi.org/10.1038/s41598-024-81332-y · Published: December 2, 2024

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

Bone marrow mesenchymal stem cells (BMMSCs) are being studied as a treatment for spinal cord injury (SCI) because they can help nerves regenerate, prevent cell death, and improve function. MicroRNAs (miRNAs) play a role in how BMMSCs help with SCI recovery, suggesting that targeting specific miRNAs could improve recovery. This study focuses on miR-202-3p, which was previously found to be involved in spinal cord repair. The study found that BMMSCs use miR-202-3p to improve motor recovery in rats with SCI, repair damaged spinal cords, and help nerve axons regenerate. At the molecular level, BMMSCs stimulate autophagy (a cellular cleaning process) and suppress neuronal apoptosis (programmed cell death) by regulating certain pathways (AMPK, MAPK, and PI3K/AKT/mTOR). This helps to foster functional recovery after SCI.

Study Duration

28 days

Participants

54 adult female Sprague–Dawley (SD) rats

Evidence Level

Not specified

Key Findings

1
BMMSCs improve motor function recovery in SCI rats, as evidenced by increased BBB scores and improved footprint analysis.
2
BMMSCs promote the histological repair of damaged spinal cords by reducing inflammation and cystic cavity size.
3
BMMSCs enhance autophagy and mitophagy, as shown by increased levels of autophagosome markers (LC3II/I, Beclin1, VPS34, CTSD) and mitophagy markers (Parkin, BNIP3, Nix).

Research Summary

This study investigates the role of bone marrow mesenchymal stem cells (BMMSCs) and miR-202-3p in treating spinal cord injury (SCI) in rats. The research demonstrates that BMMSCs, mediated by miR-202-3p, promote autophagy, suppress neuronal apoptosis, and ultimately enhance functional recovery post-SCI. The findings indicate that BMMSCs improve motor function, facilitate histological repair of the damaged spinal cord, and protect neurons from apoptosis after SCI. BMMSCs also promote axonal regeneration. The study elucidates the molecular mechanisms through which BMMSCs exert their therapeutic effects, revealing that they modulate the AMPK, MAPK, and PI3K/AKT/mTOR/TFEB pathways to stimulate mitochondrial autophagy and suppress neuronal apoptosis.

Practical Implications

Therapeutic Potential

BMMSCs could be a promising therapeutic modality for spinal cord injury.

Targeted Therapy

Targeted modulation of miR-202-3p holds potential for augmenting SCI recovery.

Pathway Modulation

Modulation of AMPK, MAPK, and PI3K/AKT/mTOR/TFEB pathways can be exploited for therapeutic interventions.

Study Limitations

1
Ethical concerns, therapeutic efficacy, complications, immune responses, and tumorigenic potential must be addressed before clinical translation of BMMSC therapy.
2
The proportion of BMMSCs identified within the spinal cord after tail vein injection is typically low.
3
The specific function of miR-202-3p requires further investigation and verification through a dual luciferase assay.

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