Perspectives in the Cell-Based Therapies of Various Aspects of the Spinal Cord Injury-Associated Pathologies: Lessons from the Animal Models

Cells, 2021 · DOI: 10.3390/cells10112995 · Published: November 3, 2021

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injury (SCI) is a severe condition that often results in significant disabilities. There is an urgent need to improve clinical treatments for SCI patients. Cell transplantation, either alone or with artificial matrices, appears to be a promising approach for improving SCI treatment. Cell-based therapies are being explored to restore function after SCI. These therapies focus on reducing inflammation, preventing neuron death, promoting axon regeneration, and rebuilding or activating surviving spinal cord networks. Researchers are examining various cell types, including Schwann cells, olfactory ensheathing cells, and stem cells like neural stem cells and mesenchymal stem cells, to find the most effective ways to repair the injured spinal cord.

Study Duration

Not specified

Participants

Animal models

Evidence Level

Review

Key Findings

1
Transplantation of mesenchymal stem cells (MSCs) into the injured spinal cord can increase the number of M2 macrophages and reduce the number of M1 macrophages, leading to functional recovery in animal models.
2
Small extracellular vesicles (sEVs) derived from MSCs can enhance the polarization of macrophages into the M2 phenotype, reducing inflammation and promoting functional recovery in spinal cord injury models.
3
Neural stem cell-derived small extracellular vesicles (NSC-sEVs) can attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy, a process that removes damaged or unnecessary cell components.

Research Summary

This review discusses recent advances in cell-based experimental strategies aimed at supporting or restoring function to the injured spinal cord, focusing on regenerative mechanisms relevant to clinical translation. Cell transplantation strategies target key aspects of SCI pathology, including inflammation, neuronal apoptosis, angiogenesis, axonal sprouting and regeneration, remyelination, and rebuilding/activating spinal cord networks. While cell-based therapies show promise, challenges remain in achieving significant functional regeneration, particularly after complete spinal cord injury, necessitating combined therapeutic strategies for improved outcomes.

Practical Implications

Therapeutic Target Identification

Highlights specific cellular and molecular targets (e.g., M1/M2 macrophage polarization, autophagy activation) for developing more effective SCI treatments.

Combination Therapies

Emphasizes the potential of combined therapeutic approaches targeting multiple aspects of SCI pathology to achieve more meaningful functional recovery.

Clinical Translation Strategies

Provides insights into regenerative mechanisms triggered by exogenous cells, guiding the development of more effective cell-based therapies for clinical application.

Study Limitations

1
The majority of pre-clinical cell-based studies were performed with rodent models.
2
The majority of attempts reported to date show very slight improvement of locomotor function.
3
The capacity of these approaches to facilitate regeneration and achieve meaningful functional recovery is rather modest when considered individually.

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