Human Mesenchymal Stem Cell Transplantation Improved Functional Outcomes Following Spinal Cord Injury Concomitantly with Neuroblast Regeneration

Adv Pharm Bull, 2023 · DOI: 10.34172/apb.2023.058 · Published: October 20, 2023

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Spinal cord injury (SCI) results in neuronal loss, glial scar formation, and axonal injury, potentially leading to long-lasting disability. Transplantation of stem cells may promote neuroprotective molecules and reprogramming of astrocytes into neuroblasts. Mesenchymal stem cells (MSCs) can secrete essential materials for neuroprotection, potentially inducing neuronal cell replacement, remyelination, angiogenesis, and reduced inflammation. Human amniotic fluid-derived MSCs (hAF-MSCs) are considered due to their amnion origin and expression of pluripotency markers. These cells exhibit high proliferative and regenerative potential. MSCs can secrete paracrine factors in the form of a conditioned medium (CM) containing growth factors and anti-inflammatory agents. The SRY (sex-determining region Y-box 2), or Sox2, is essential for maintaining pluripotency of embryonic stem cells and directs neural differentiation. Sox2 can mediate the reprogramming of astrocytes to doublecortin (DCX)+ neuroblasts, potentially treating SCI by converting glial cells to mature neurons.

Study Duration

Not specified

Participants

54 adult male Wister rats

Evidence Level

Not specified

Key Findings

1
MSCs increased the number of endogenous DCX-positive cells and decreased the number of GFAP-positive cells via juxtacrine and paracrine mechanisms.
2
Transplanted human astrocytes were converted to neuroblasts rather than astrocytes under the influence of MSCs and CM in SCI.
3
Functional recovery indexes were promoted in groups that received MSCs and CM.

Research Summary

The study investigates the potential of human amniotic fluid mesenchymal stem cells (hAF-MSCs) and their conditioned medium (CM) to promote neuroblast and astrocyte production and functional recovery following spinal cord injury (SCI) in rats. The results indicate that MSCs, through juxtacrine and paracrine pathways, can direct spinal cord endogenous neural stem cells (NSCs) to the neuroblasts lineage, increasing DCX-positive cells and declining astrocytes. The research points out the protective and regenerative potential of MSCs in SCI through the development of DCX-positive cells and conversion of astrocytes to neuroblasts, mediated by juxtacrine activity and paracrine effects.

Practical Implications

Therapeutic Potential

MSCs and CM could be relevant tools in regenerative medicine for spinal cord injury, promoting neurogenesis and reducing glial scar formation.

Reprogramming Strategies

Focusing on in vivo reprogramming of endogenous astrocytes to neuroblasts can be a promising therapeutic strategy.

Delivery Methods

Both direct transplantation of MSCs and infusion of CM demonstrate potential benefits, with MSCs showing greater efficacy in some aspects.

Study Limitations

1
Cellular and molecular mechanisms underlying cellular reprogramming is not fully understood
2
The effect of the MSCs was more in comparison to CM
3
More complementary studies should be done to address all aspects of the reprogramming subject

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