Inflammatory stimulation of astrocytes affects the expression of miRNA‑22‑3p within NSCs‑EVs regulating remyelination by targeting KDM3A

Stem Cell Research & Therapy, 2023 · DOI: https://doi.org/10.1186/s13287-023-03284-w · Published: March 13, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injury (SCI) leads to nerve cell death and demyelination, hindering functional recovery. Endogenous neural stem cells (NSCs) offer a potential treatment strategy due to their ability to differentiate into mature nerve cells. Inflammation following SCI involves astrocytes, which can transform and release cytokines affecting pathology. Extracellular vesicles (EVs) mediate cell-cell communication, and NSC-derived EVs can promote neurological recovery. This study explores how cytokines from inflammation-stimulated astrocytes affect NSC differentiation and communication, revealing a BMP-miRNA-22-TGF-β regulatory loop that maintains glial balance and prevents excessive astrocytic scars.

Study Duration

4 weeks

Participants

SD rats

Evidence Level

Not specified

Key Findings

1
Inflammatory stimulation of astrocytes increases BMP2 release, promoting NSC differentiation into astrocytes and inhibiting axon remyelination in SCI lesions.
2
BMP2 enrichment also leads to miRNA-22-3p enrichment within NSC-derived extracellular vesicles (EVs).
3
miRNA-22 molecules function as a feedback loop, promoting NSC differentiation into oligodendrocytes and remyelination by targeting KDM3A.

Research Summary

This study investigates the effects of cytokines released from inflammation-stimulated astrocytes on the differentiation of NSCs following SCI and explores the influence of these cytokines on NSC–NSC communication. The researchers demonstrated that inflammatory stimulation promotes astrocytes to release more BMP2, which directly promoted the differentiation of NSCs into astrocytes, leading to the failure of axon regrowth. The cytokines released from inflammatory stimulated astrocytes enrich miRNA-22-3p within NSC-EVs, mediating NSC differentiation into oligodendrocytes by targeting KMD3A and repressing the TGF-β signaling pathway.

Practical Implications

Therapeutic target identification

The BMP2-miRNA-22-KDM3A/TGF-β axis represents a potential therapeutic target for promoting remyelination and neurological recovery after SCI.

EV-based therapies

NSC-derived EVs, particularly those enriched with miRNA-22-3p, could be developed as a cell-free therapeutic approach to enhance remyelination.

Inflammation management

Controlling the inflammatory response and astrocyte activation post-SCI may improve the microenvironment for NSC differentiation and axon regeneration.

Study Limitations

1
The study primarily focuses on in vitro and in vivo rat models, and further research is needed to validate these findings in human subjects.
2
The precise mechanisms by which BMP2 regulates miRNA-22-3p expression in NSCs-EVs require further investigation.
3
The study does not explore the long-term effects of miRNA-22-3p modulation on neurological recovery after SCI.

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