Progression of mesenchymal stem cell regulation on imbalanced microenvironment after spinal cord injury

Stem Cell Research & Therapy, 2024 · DOI: https://doi.org/10.1186/s13287-024-03914-x · Published: January 1, 2024

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

Spinal cord injury (SCI) results in significant neural damage and inhibition of axonal regeneration due to an imbalanced microenvironment. Mesenchymal stem cell (MSC) transplantation is a therapeutic approach for SCI. This review focuses on MSC regulation of the microenvironment following SCI, covering inflammation, neurotrophy, and axonal regeneration. Following SCI, the destruction of neurons, glial cells, and disruption of the surrounding environment have been observed. A novel perspective on the imbalance of the microenvironment after SCI is aimed to be offered, focusing on inflammation, nutrient supply, and regeneration ability. MSCs have a powerful paracrine ability to improve the imbalanced microenvironment, are easily cultured, target lesion sites precisely, and have low immunogenicity and tumorigenicity. This review elucidates the comprehensive mechanism by which MSCs regulate the imbalanced microenvironment following SCI.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
MSCs interact with immune cells through soluble secretions or direct cell communication to modulate the metabolic activities of inflammatory cells, influencing their function within the inflammatory microenvironment.
2
MSCs can secrete neurotrophic factors to ameliorate imbalances after SCI. An increase of BDNF, NGF and glial cell-derived neurotrophic factor (GDNF) has been observed after transplantation.
3
Following transplantation of MSCs, a significant presence of growth cone-like structures occurs, partially attributed to the regulation of RhoA/ROCK and PTEN/mTOR pathway. MSCs inhibit retraction bulb formation and make an orderly growth cone.

Research Summary

SCI leads to neural impairment, tissue destruction, inflammatory cascades, and imbalances in the nutrient microenvironment. Glial scar formation and insufficient intrinsic mechanisms hinder axonal regeneration. MSCs modulate the microenvironment, mitigating inflammation and improving the inhibitory environment. MSCs are a promising therapeutic approach, modulating the imbalanced microenvironment through paracrine abilities and direct cellular communication. They mitigate inflammation, restore nutrient balance, and improve the inhibitory microenvironment, resulting in axon regeneration and neurological function recovery. MSC application methods, such as exosomes, modification, and combination with biomaterials, have been explored. A comprehensive understanding of MSC regulation on the imbalanced microenvironment following SCI is crucial for precision and targeted regulation.

Practical Implications

Clinical Translation Strategies

Highlights the importance of standardizing MSC production and optimizing transplantation strategies (timing, dose, route) to improve clinical outcomes.

Combination Therapies

Suggests integrating MSC transplantation with other approaches like immunotherapy and biomaterials to achieve comprehensive clinical rehabilitation.

Targeted MSC Modification

Focuses on the need for specific genetic or preconditioning modifications to tailor MSCs to different injury stages and microenvironments for enhanced therapeutic effects.

Study Limitations

1
Current animal models, mainly rodents, may not accurately reflect human SCI pathology.
2
Inadequate translational studies and clinical trials hinder the widespread implementation of MSC therapy.
3
Ethical boundaries and risk assessment concerning MSC transplantation remain unresolved, especially regarding antigenicity and tumorigenicity.

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