Mechanism of mesenchymal stem cells in spinal cord injury repair through macrophage polarization

Cell Biosci, 2021 · DOI: https://doi.org/10.1186/s13578-021-00554-z · Published: January 1, 2021

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

Spinal cord injury (SCI) is a serious complication of spine injury, which often leads to serious dysfunction of the limbs below the injured segment. It is one of the most common diseases leading to disability, and no effective treatments have been developed. Inflammatory reactions occurring after SCI are related to various functions of immune cells over time at different injury sites. Macrophages are important mediators of inflammatory reactions and are divided into two different subtypes (M1 and M2), which play important roles at different times after SCI. Mesenchymal stem cells (MSCs) are characterized by multi-differentiation and immunoregulatory potentials, and different treatments can have different effects on macrophage polarization. MSC transplantation has become a promising method for eliminating nerve injury caused by SCI and can help repair injured nerve tissues.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Level 5, Review

Key Findings

1
MSCs can regulate macrophage polarization by secreting soluble proteins, including ILs and chemokines, which ultimately relieve SCI.
2
MSC-exos also alleviate SCI by participating in macrophage polarization. In an SCI model, MSC-exos promoted functional recovery by inducing the mRNA expression of M2 macrophage markers, including CD206, IL-10, and Arg-1, and facilitated bone marrow-derived macrophage polarization from an M1 to an M2 phenotype.
3
Hypoxic pretreatment of MSCs (to simulate the hypoxic environment in the body) can significantly improve their biological functions and activities, thereby improving the efficacy of treatment in various disease models

Research Summary

A series of pathophysiological changes occur after SCI. The primary injury is related to the destruction of axons and neurons. The secondary injury is caused by nerve inflammation, which directly or indirectly controls the sequelae of SCI and can lead to morphological edema, cavitation, and reactive glial hyperplasia. Given that the immune response in SCI is a “double-edged sword,” beneficial aspects should be promoted during treatment, rather than completely inhibiting inflammation. The pro-inflammatory and anti-inflammatory effects of macrophages during different stages of SCI are important causes of symptoms at different periods. MSCs have great potential for spinal cord repair and represent promising candidates for long-term treatment of secondary SCI, caused by neuroinflammation.

Practical Implications

Therapeutic Potential

MSC transplantation and MSC-derived exosomes show promise in promoting functional recovery after SCI by modulating macrophage polarization.

Targeted Therapies

Understanding the specific soluble factors and signaling pathways involved in MSC-macrophage interaction can lead to the development of targeted therapies to enhance SCI repair.

Optimized MSC Treatment

Preconditioning MSCs with hypoxia may improve their therapeutic efficacy, providing a basis for optimizing MSC-based treatments for SCI.

Study Limitations

1
Low survival rate of transplanted MSCs in the spinal cord.
2
Potential differentiation of MSCs into unwanted cell types, such as osteoblasts.
3
Lack of exocrine-production capacity and low targeting limits direct application of exocrine secretions as a therapeutic agent.

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