Multipotent Mesenchymal Stem Cell-Based Therapies for Spinal Cord Injury: Current Progress and Future Prospects

Abstract

Spinal cord injury (SCI) represents a significant medical challenge, often resulting in permanent disability and severely impacting the quality of life for affected individuals. Traditional treatment options remain limited, underscoring the need for novel therapeutic approaches. In recent years, multipotent mesenchymal stem cells (MSCs) have emerged as a promising candidate for SCI treatment due to their multifaceted regenerative capabilities. This comprehensive review synthesizes the current understanding of the molecular mechanisms underlying MSC-mediated tissue repair in SCI. Key mechanisms discussed include neuroprotection through the secretion of growth factors and cytokines, promotion of neuronal regeneration via MSC differentiation into neural cell types, angiogenesis through the release of pro-angiogenic factors, immunomodulation by modulating immune cell activity, axonal regeneration driven by neurotrophic factors, and glial scar reduction via modulation of extracellular matrix components. Additionally, the review examines the various clinical applications of MSCs in SCI treatment, such as direct cell transplantation into the injured spinal cord, tissue engineering using biomaterial scaffolds that support MSC survival and integration, and innovative cell-based therapies like MSC-derived exosomes, which possess regenerative and neuroprotective properties. As the field progresses, it is crucial to address the challenges associated with MSC-based therapies, including determining optimal sources, intervention timing, and delivery methods, as well as developing standardized protocols for MSC isolation, expansion, and characterization. Overcoming these challenges will facilitate the translation of preclinical findings into clinical practice, providing new hope and improved treatment options for individuals living with the devastating consequences of SCI.

Keywords: angiogenesis; multipotent mesenchymal stem cells; neuronal regeneration; neuroprotection; regenerative medicine; spinal cord injury.

Figure 1

Overview of stem cell classifications based on differentiation potential and developmental stages. Stem cells are classified based on their differentiation potential, which reflects their ability to form various cell types. Totipotent stem cells, found in early-stage embryos, can differentiate into all three germ layers, as well as extra-embryonic tissues and placental cells. Pluripotent stem cells, present in the blastocyst stage of development, maintain the ability to self-renew and differentiate into the three germ layers and multiple lineages but cannot form extra-embryonic tissues or placental cells. Multipotent stem cells, also known as adult or somatic stem cells, are undifferentiated cells found in postnatal tissues. These specialized cells have limited self-renewal capabilities and are committed to specific lineages. Unipotent stem cells are the most restricted in their differentiation potential, as they can only give rise to a single cell type, although they still retain the capacity for self-renewal.