Molecular Mechanisms and Clinical Application of Multipotent Stem Cells for Spinal Cord Injury

Cells, 2023 · DOI: https://doi.org/10.3390/cells12010120 · Published: December 28, 2022

Spinal Cord Injury Regenerative Medicine & Stem Cells

Simple Explanation

Spinal Cord Injury (SCI) often leads to lasting disabilities because standard treatments can only do so much to help recover lost functions. Stem cell therapy is being explored as a new way to potentially regenerate the injured spinal cord, using the special abilities of stem cells. Multipotent stem cells, like mesenchymal, neural, and hematopoietic stem cells, are the most studied types for SCI treatment. The environment around the injury affects how well these transplanted stem cells survive and work. Understanding how SCI changes the body and how stem cells work at a molecular level could lead to better treatments. This includes using stem-cell-derived exosomes, genetically modified stem cells, scaffolds, and nanomaterials to improve how stem cells help the spinal cord regenerate.

Study Duration

Not specified

Participants

Review article; clinical trials mentioned vary in participant numbers.

Evidence Level

Review

Key Findings

1
MSCs reach the lesion site through the chemotactic mechanism known as a homing effect, which is important for therapy effectiveness.
2
The differentiation capability of MSCs probably plays a secondary role in functional recovery in patients with SCI; rather, benefits result from paracrine and immunomodulatory activity.
3
HSCs exert their therapeutic activity through differentiation and releasing numerous cytokines and neurotrophic factors, potentially transforming into astrocytes, neuroprotective glia, and oligodendrocytes.

Research Summary

This review explores the molecular mechanisms of action of multipotent stem cells (MSCs, NSCs, and HSCs) and their clinical efficacy in treating SCI. It discusses the pathogenesis of SCI, optimal stem cell administration protocols, and recent therapeutic approaches based on or combined with SCT. MSCs are characterized by easy extraction, rapid proliferation, and can be obtained from the patients themselves, making them promising for SCI therapy, primarily through paracrine and immunomodulatory effects rather than direct differentiation. Novel therapeutic approaches based on stem cell therapy, such as stem-cell-derived exosomes, gene-modified stem cells, and biomaterials, aim to enhance the effectiveness of SCT by addressing limitations like immune rejection and poor cell survival in the SCI microenvironment.

Practical Implications

Refine Administration Protocols

Further research should focus on establishing optimal stem cell administration protocols, including dosage, timing, and route of administration, to maximize therapeutic efficacy in SCI patients.

Develop Combination Therapies

Combine stem cell therapy with other regenerative approaches, such as biomaterials, growth factors, and rehabilitation strategies, to promote synergistic effects and improve functional outcomes after SCI.

Enhance Stem Cell Properties

Explore genetic modification and exosome-based therapies to enhance stem cell survival, differentiation, and paracrine signaling, thereby improving their therapeutic potential for SCI treatment.

Study Limitations

1
Lack of well-designed, randomized, controlled studies on a large group of patients.
2
High heterogeneity in dosing, transplantation phase, and route of administration across clinical studies.
3
The exact molecular mechanism of action through which HSCs exert their neuroregenerative properties in the treatment of SCI remains not thoroughly investigated

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