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RVG-Modified BMSCs-Derived Small Extracellular Vesicles Loaded With miR-21 Alleviate Neuronal Injury Resulted From
Yiyang Li1,2, Jiacheng Hu1,2, Jinfen Chen1,2
1State Key Laboratory of Mechanism and Quality of Chinese Medicine, University of Macau, Taipa, Macau SAR, China.
Journal of Extracellular Vesicles
|May 6, 2026
Summary
Engineered stem cell-derived vesicles carrying miR-21 effectively target the brain to treat ischemic stroke by suppressing neuronal autophagy and apoptosis. This approach enhances neurological function and reduces brain damage.
Area of Science:
- Biomedical Engineering
- Neuroscience
- Regenerative Medicine
Background:
- Ischemic stroke (IS) causes significant disability and mortality with limited treatment options.
- Bone marrow mesenchymal stem cell-derived small extracellular vesicles (BMSC-sEVs) show therapeutic potential for IS but face challenges crossing the blood-brain barrier (BBB) and delivering sufficient microRNA (miRNA).
Purpose of the Study:
- To develop brain-targeting BMSC-sEVs engineered to overexpress miR-21 for enhanced IS therapy.
- To investigate the therapeutic efficacy and underlying mechanisms of these engineered vesicles in an IS mouse model.
Main Methods:
- Bioengineered BMSCs overexpressing miR-21 and displaying RVG-Lamp2b peptide on sEVs surface.
- Characterization of RVG-miR21-sEVs, assessment of neuronal targeting, and evaluation in a mouse transient middle cerebral artery occlusion (tMCAo) model.
- Investigation of cellular mechanisms including autophagy, mitochondrial function, apoptosis, and the PTEN/Akt/mTOR pathway.
Main Results:
- RVG-miR21-sEVs demonstrated enhanced neuronal affinity and superior neurological functional recovery and reduced cerebral infarction in the tMCAo model.
- Treatment with RVG-miR21-sEVs suppressed neuronal autophagy, mitochondrial dysfunction, and apoptosis post-oxygen-glucose deprivation/re-oxygenation (OGD/R).
- miR-21 was confirmed to target PTEN, antagonizing neuronal injury via the PTEN/Akt/mTOR pathway.
Conclusions:
- RVG-modified, miR-21-overexpressing BMSC-sEVs represent a promising strategy for IS treatment by improving brain targeting and miRNA delivery.
- This engineered sEV therapy effectively mitigates ischemic brain injury by modulating autophagy and apoptosis through the miR-21/PTEN/Akt/mTOR axis.
