Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

PNAS, 2017 · DOI: 10.1073/pnas.1616340114 · Published: January 13, 2017

Spinal Cord Injury Neurology Regenerative Medicine & Stem Cells

Simple Explanation

The study explores a new method to help the spinal cord heal after an injury, using human stem cells and a special support structure. They found that this approach helps the stem cells survive and work better, leading to improved movement and less pain in rats with spinal cord injuries. The support structure, made of a safe material, helps the stem cells have multiple beneficial effects, such as protecting nerve cells, encouraging new blood vessel growth, and reducing inflammation. This combination of effects helps restore the connections needed for movement. This research suggests that the injured spinal cord can use different pathways than normal to recover, opening new possibilities for treating spinal cord injuries in people.

Study Duration

4 weeks

Participants

Female adult Sprague-Dawley rats (n=7 per group)

Evidence Level

Not specified

Key Findings

1
PLGA scaffolding augments hMSC stemness, engraftment, and function without neural transdifferentiation or mesenchymal lineage development.
2
Scaffolded hMSC-derived neurotrophism, neurogenesis, angiogenesis, antiautoimmunity, and antiinflammation support the propriospinal network, neuromuscular junctions, and serotonergic reticulospinal reinnervation to activate the central pattern generator for restoring hindlimb locomotion.
3
The injured spinal cord may deploy polysynaptic neural circuits different from normal adulthood pathways for postinjury improvement.

Research Summary

The study developed a platform technology using hMSCs and a PLGA matrix to improve donor cell survival and localized engraftment in vivo. The synthetic matrix supports hMSC survival, stemness, and function, while avoiding phenotypic differentiation and tumorigenesis in the lesioned spinal cord. The scaffolded hMSCs robustly restore locomotor function and prevent neuropathic pain by various mechanisms, including mitigating T-cell-mediated demyelination and augmenting M2 macrophage polarization.

Practical Implications

Therapeutic Potential

The scaffolded hMSC approach shows promise for treating spinal cord injuries by promoting tissue repair, reducing inflammation, and restoring neural connections.

Clinical Translation

The use of a clinically safe PLGA scaffold and autologous hMSCs suggests potential for translation to human clinical trials.

Recovery Neurobiology

The findings support the concept that the injured spinal cord can utilize alternative neural circuits for functional recovery, informing future therapeutic strategies.

Study Limitations

1
The T9–T10 lesion paradigm does not directly model spinal cord contusion, the most common SCI seen clinically.
2
The study primarily focuses on mechanisms in rats; further research is needed to confirm these findings in humans.
3
Long-term effects and safety of the hMSC implantation need further investigation.

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