Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury

Journal of Inflammation Research, 2022 · DOI: https://doi.org/10.2147/JIR.S349572 · Published: January 26, 2022

Spinal Cord Injury Immunology Regenerative Medicine & Stem Cells

Simple Explanation

Spinal cord injury (SCI) often leads to loss of motor and sensory functions. The secondary injury phase, characterized by inflammation, significantly hinders recovery. Mesenchymal stem cells (MSCs) have shown promise in regulating this inflammation. MSCs can modulate the behavior of immune cells like macrophages, astrocytes, and T lymphocytes, which are key players in neuroinflammation. By influencing these cells, MSCs create a supportive environment for tissue repair. This review explores how MSC transplantation can be used to control immune cells and develop new therapies for SCI, emphasizing the importance of understanding interactions between immune cells and MSCs.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Level: Review

Key Findings

1
MSCs can regulate macrophage polarization, shifting the balance from pro-inflammatory M1 to anti-inflammatory M2 phenotypes, which promotes axonal regeneration and reduces glial scar formation.
2
MSCs can inhibit the activation of A1 astrocytes, which are neurotoxic, and promote the formation of A2 astrocytes, which support neuronal restoration and survival.
3
MSCs can modulate T cell responses by suppressing Th1 and Th17 cell differentiation and inducing the formation of Treg cells, leading to a reduction in pro-inflammatory cytokines.

Research Summary

This review highlights the critical role of inflammation in secondary spinal cord injury (SCI) and the potential of mesenchymal stem cells (MSCs) to modulate this inflammation. MSCs exert immunomodulatory effects on key immune cells involved in SCI, including macrophages, astrocytes, and T lymphocytes, promoting a regenerative microenvironment. Preconditioning strategies and genetic modification of MSCs may further enhance their therapeutic efficacy in SCI by improving their survival and immunomodulatory capacity.

Practical Implications

Therapeutic Target Identification

Identifying specific regulatory factors and pathways involved in MSC-mediated immune cell modulation can lead to the development of targeted therapies for SCI.

Clinical Translation

Further research is needed to determine the optimal conditions for MSC transplantation, including cell source, dosage, timing, and route of administration, to improve clinical outcomes.

Enhanced MSC Therapies

Exploring preconditioning and genetic modification strategies can enhance MSC survival and immunomodulatory capacity, potentially leading to more effective SCI treatments.

Study Limitations

1
Current in vivo models are mainly small rodents, which may not fully represent the human condition.
2
Safety concerns remain regarding the use of genetically modified MSCs due to the risk of tumorigenesis.
3
The optimal number of cells, cell source, timing, and route of administration for MSC transplantation need further investigation.

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