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Updated: Oct 12, 2025
Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Bone marrow mesenchymal stem cell derived exosomal miR-455-5p protects against spinal cord ischemia reperfusion
Bing Liu1, Wenjun Zheng2, Li Dai3
1Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China; Department of Vascular Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
Abstract:
At present, much more studies have focused on the therapeutic effect of exosome-delivered microRNAs on diseases. Previous study has shown that miR-455-5p is downregulated in ischemic stroke, but little is known about the role of exosome-delivered miR-455-5p in spinal cord ischemia reperfusion (SCIR) injury. Herein, we isolated exosomes from bone marrow mesenchymal stem cells (BMSCs) transfected with lentivirus vectors containing miR-455-5p. SCIR rat model was established after the intrathecal injection of exosomes containing miR-455-5p. The expression level of miR-455-5p was downregulated after SCIR, administration of exosomal miR-455-5p enhanced the level of miR-455-5p in the injured spinal cord. Hind-limb motor function scores indicated that exosomal miR-455-5p improved the recovery of hind-limb function of SCIR rats. HE staining and Nissl staining showed that miR-455-5p enriched exosomes reduced histopathological abnormalities after SCIR. Double immunofluorescence staining revealed that exosomes containing miR-455-5p reduced apoptosis of neurons, and activated autophagy in neurons after SCIR. We observed that the expression of Nogo-A, a direct target of miR-455-5p, was decreased in the spinal cord of exosomal miR-455-5p administrated SCIR rats. Targeting relationship between miR-455-5p and Nogo-A was verified by dual-luciferase reporter assay. In summary, exosomes containing miR-455-5p had the neuroprotective effects on SCIR injury by promoting autophagy and inhibiting apoptosis of neurons.
Insights
Exosomes carrying miR-455-5p protect against spinal cord ischemia reperfusion (SCIR) injury. This therapy enhances motor function recovery by reducing neuronal apoptosis and activating autophagy.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Molecular Biology
Background:
- MicroRNAs (miRNAs) delivered via exosomes show therapeutic potential for various diseases.
- miR-455-5p is downregulated in ischemic stroke, but its role in spinal cord ischemia reperfusion (SCIR) injury remains unclear.
Purpose of the Study:
- To investigate the therapeutic effect of exosome-delivered miR-455-5p on SCIR injury in a rat model.
- To elucidate the underlying mechanisms of neuroprotection.
Main Methods:
- Bone marrow mesenchymal stem cell (BMSC)-derived exosomes were engineered to overexpress miR-455-5p using lentivirus vectors.
- A rat model of SCIR was established, followed by intrathecal injection of engineered exosomes.
- Histopathological analysis (HE, Nissl staining), motor function assessment, immunofluorescence, and dual-luciferase reporter assay were performed.
Main Results:
- Administration of exosomal miR-455-5p increased miR-455-5p levels in the injured spinal cord.
- Exosomal miR-455-5p significantly improved hind-limb motor function recovery in SCIR rats.
- Histological examination revealed reduced damage, decreased neuronal apoptosis, and activated autophagy in the injured spinal cord.
- Nogo-A, a direct target of miR-455-5p, was found to be downregulated.
Conclusions:
- Exosomes engineered to deliver miR-455-5p exert significant neuroprotective effects against SCIR injury.
- This therapeutic strategy promotes autophagy and inhibits apoptosis in neurons, leading to functional recovery.
- Targeting Nogo-A via miR-455-5p is a key mechanism in the observed neuroprotection.
