Neuroinﬂammation and Scarring After Spinal Cord Injury: Therapeutic Roles of MSCs on Inﬂammation and Glial Scar

Frontiers in Immunology, 2021 · DOI: 10.3389/fimmu.2021.751021 · Published: December 2, 2021

Spinal Cord Injury Immunology Regenerative Medicine & Stem Cells

Simple Explanation

Spinal cord injuries often lead to permanent disabilities due to the formation of glial scars, which hinder nerve regeneration. A persistent inflammatory response, caused by interactions between immune cells, further complicates recovery. Current therapies aim to reduce this inflammation, particularly in the subacute and chronic phases after the initial acute response. Mesenchymal stem cells (MSCs) have emerged as a promising cell therapy for SCI. Transplantation of MSCs has demonstrated the ability to reduce both excessive glial scar formation and inflammatory responses, thereby improving anatomical and functional recovery. This review explores the impact of inflammatory responses and glial scar formation on spinal cord injury and repair. It also examines the role of MSCs in modulating neuroinflammation and glial scar formation following SCI.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Early inflammatory responses after SCI can be beneficial for clearing debris and elevating neurotrophic factors. However, sustained inflammation leads to the release of inflammatory cytokines and reactive oxygen species, causing further damage.
2
Glial scars, while initially protective, can become physical barriers to axon regeneration due to components like chondroitin sulfate proteoglycans (CSPGs).
3
MSCs transplantation can modulate the immune response by promoting anti-inflammatory cells (M2 macrophages, A2 astrocytes, Tregs, and Th2 cells) and inhibiting pro-inflammatory responses, which can protect neurons and promote nerve regeneration.

Research Summary

This review discusses the dual role of inflammation and glial scar formation in spinal cord injury (SCI) prognosis. While early inflammation is beneficial for clearing debris, persistent inflammation exacerbates secondary injury. Similarly, glial scars initially protect but later impede axonal regeneration. Mesenchymal stem cells (MSCs) have shown promise as a therapeutic strategy for SCI by modulating neuroinflammation and glial scar formation. MSCs can shift the immune response toward an anti-inflammatory state and promote axonal regeneration. Clinical trials of MSCs for SCI are underway, with preliminary results suggesting safety and potential efficacy. However, challenges remain in optimizing MSC therapy, including determining the optimal source, administration route, and potential long-term effects.

Practical Implications

Therapeutic Target Identification

Further research into the specific mechanisms by which MSCs regulate inflammation and glial scar formation post-SCI could lead to the identification of novel therapeutic targets.

Clinical Translation Optimization

Clinical trials should focus on optimizing MSC therapy, including determining the optimal source, administration route, and dosage.

Personalized Medicine

Future research should investigate preconditioning MSCs with certain stimuli before transplantation to enhance their immunomodulatory ability and tailor treatments to individual patients.

Study Limitations

1
Long-term tumorigenicity of MSCs needs further observation.
2
Studies on the MSCs therapy focus on the acute and subacute phages post-SCI, while the therapeutic effect in the chronic phage still needs to be confirmed.
3
The quality and safety of MSCs from different laboratories vary greatly, so there is an urgent need to develop general guidelines for the preparation and storage of MSCs.

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