Regenerative Potential of Injured Spinal Cord in the Light of Epigenetic Regulation and Modulation

Cells, 2023 · DOI: 10.3390/cells12131694 · Published: June 22, 2023

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

A spinal cord injury (SCI) is a physical harm that often leads to permanent paralysis in mammals. Restoring the spinal cord's function is difficult because it doesn't regenerate well. However, some species like axolotls and zebrafish can regenerate their spinal cords after injury. Epigenetic control, involving DNA methylation, histone modifications, and microRNAs, plays a crucial role in spinal cord regeneration. This review compares epigenetic mechanisms in spinal cord injuries between non-regenerating and regenerating species. Extracellular vesicles (EVs) are also discussed for their potential role in spinal cord injury and as targets for therapeutic intervention. EVs can carry a range of bioactive cargo that may be modified in response to external stimuli after injury.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
In mammals, axonal regrowth after a spinal cord injury is hindered by the development of a glial scar that mainly consists of reactive astrocytes and proteoglycans.
2
In zebraﬁsh, spinal cord injury responses tend to result in injury healing and functional recovery, unlike in mammals. These include a brief inflammatory reaction, macrophage involvement, limited cell loss, permissive axonal regrowth conditions, and neurogenesis.
3
Extracellular vesicles (EVs) play a critical role in intercellular communication and epigenetic regulation by transporting biomolecules that influence the recipient cell’s gene expression after spinal cord injury.

Research Summary

This review provides a comparative analysis of spinal cord injury in both non-regenerating (mammals) and regenerating animals (axolotl, Xenopus, zebrafish), focusing on the epigenetic mechanisms underlying repair and regeneration. In mammals, SCI leads to glial scar formation, hindering axonal regrowth, while in regenerative species like zebrafish, there is a brief inflammatory response, permissive axonal regrowth, and neurogenesis. The review discusses the potential of extracellular vesicles (EVs) as therapeutic vehicles for delivering cargo to target cells in spinal cord injuries and their role in epigenetic regulation by transferring miRNAs and other biomolecules.

Practical Implications

Biomarker Development

Epigenetic networks can be used to develop biomarkers for predicting prognosis and clinical assessment of SCI.

Cell Transplantation Enhancement

Epigenetic manipulation can control neural stem/precursor cells (NS/PCs) and their microenvironments to facilitate neuronal differentiation and axon elongation, improving functional recovery.

EV-Based Therapies

Extracellular vesicles (EVs) can be used to deliver therapeutic agents to the injury site, promoting nerve regeneration and improving functional recovery. They can also serve as a diagnostic tool.

MicroRNA therapeutics

MicroRNAs can potentially be a new class of therapeutic medicines.

Gene Therapy

Manipulating the expression of regeneration-associated genes can boost axon regeneration after damage.

Study Limitations

1
The epigenetic mechanisms behind repair and regeneration processes in both non-regenerating and regenerating animals remain unclear.
2
There are potential issues with miRNA therapeutics, such as high-dose-associated side effects and toxicity when administered in vivo.
3
Research investigating the therapeutic value of EVs in spinal cord injury is scarce.

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