A Novel Magnetic Responsive miR-26a@SPIONs-OECs for Spinal Cord Injury: Triggering Neural Regeneration Program and Orienting Axon Guidance in Inhibitory Astrocytic Environment

Advanced Science, 2023 · DOI: 10.1002/advs.202304487 · Published: October 3, 2023

Regenerative Medicine Neurology Biomedical

Simple Explanation

This research addresses the challenge of promoting directional axonal regeneration after spinal cord injury (SCI) by developing a pro-regeneration system using olfactory ensheathing cells (OECs) engineered with miR-26a-loaded superparamagnetic iron oxide nanoparticles (SPIONs). These miR-26a@SPIONs-OECs respond to magnetic fields (MF), enhancing nerve regeneration. The application of a magnetic field stimulates these cells to release extracellular vesicles (EVs) rich in miR-26a, which encourages axon growth by inhibiting specific signaling pathways in neurons. The cells also tend to migrate and orient along the magnetic field direction, potentially facilitating neuronal reconnection. Furthermore, the miR-26a-enriched EVs interact with host astrocytes, reducing inhibitory cues for neurite growth. In a rat model of SCI, this system significantly improved morphological and motor function recovery, offering insights into engineering exogenous cells with multiple cues to enhance nerve regeneration in a hostile environment.

Study Duration

8 weeks

Participants

SD rats (220−240 g)

Evidence Level

Not specified

Key Findings

1
miR-26a@SPIONs-OECs, when stimulated by a magnetic field, release extracellular vesicles rich in miR-26a, which inhibits PTEN and GSK-3β signaling pathways in neurons, promoting axon growth.
2
These engineered cells migrate and orient along the direction of an applied magnetic field, facilitating directional neurite elongation and potentially improving neuronal reconnection.
3
miR-26a-enriched EVs from miR-26a@SPIONs-OECs interact with host astrocytes, diminishing inhibitory cues for neurite growth and creating a more favorable environment for regeneration.

Research Summary

This study introduces a pro-regenerative system, miR-26a@SPIONs-OECs, designed to provide external bioactive cues to encourage linear axonal growth, moderate local astrocyte activation, and ultimately improve both morphological and functional recovery following SCI. The engineered OECs with miR-26a-loaded SPIONs show a high sensitivity to magnetic ﬁelds (MF), oﬀering synergistic multimodal cues to enhance neuronal regeneration under MF. In a rat model of SCI, the miR-26a@SPIONs-OECs system led to signiﬁcantly improved morphological and motor function recovery.

Practical Implications

Therapeutic Potential for SCI

The miR-26a@SPIONs-OECs system offers a potential therapeutic approach for treating spinal cord injuries by promoting nerve regeneration and functional recovery.

Cell Engineering Advancement

The study provides insights into engineering exogenous cells with multiple cues to augment their efficacy for stimulating and guiding nerve regeneration within a hostile astrocytic scar.

Application to Other Disorders

The strategy employed in this study is not limited to OECs for SCI but can be applied to other cells frequently used for numerous systemic disorders in clinics, including stem cells.

Study Limitations

1
The mechanism underlying the miR-26a-mediated eﬀect on astrocytes was not explored
2
Optimal SPIONs concentration and MF intensity need further clarification for disease-specific requirements
3
Additional bioactive cues that synergistically regulate inflammation in early stages and promote nerve growth in subsequent stages are yet to be explored

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