Neural stem cell delivery via porous collagen scaffolds promotes neuronal differentiation and locomotion recovery in spinal cord injury

npj Regenerative Medicine, 2020 · DOI: 10.1038/s41536-020-0097-0 · Published: January 1, 2020

Regenerative Medicine Neurology Biomedical

Simple Explanation

Neural stem cell (NSC) grafts have shown promise in animal models of spinal cord injury (SCI), but their clinical use is still limited. The matrix supporting these NSC grafts plays a vital role in their effectiveness. This study demonstrates that porous collagen-based scaffolds (PCSs) can deliver and protect embryonic NSCs at SCI sites, leading to significant improvement in locomotion recovery in mice. NSC-seeded PCS grafts enhance neuronal differentiation and integration, promote axonal elongation, and reduce astrogliosis, suggesting that using PCS to deliver NSCs could improve NSC-based SCI therapies.

Study Duration

12 weeks

Participants

Mice (male C57/BL6, 1.5–2 months old)

Evidence Level

Not specified

Key Findings

1
Porous collagen scaffolds (PCS) seeded with NSCs significantly improved locomotion recovery in mice with dorsal column crush SCI, with performance approaching that of uninjured animals after 12 weeks.
2
NSC-seeded PCS grafts increased axonal elongation at the injury site and reduced astrogliosis, both crucial for functional recovery after SCI.
3
The PCS grafts safely delivered embryonic NSCs to the SCI lesion, enabling their differentiation into both neurons and astrocytes in vivo, a prerequisite for NSC-based SCI treatments.

Research Summary

This study investigates the use of porous collagen-based scaffolds (PCSs) for delivering neural stem cells (NSCs) to spinal cord injury (SCI) sites to promote regeneration. The findings show that PCS grafts can effectively deliver and protect embryonic NSCs, enhance neuronal differentiation and integration, facilitate axonal elongation, and reduce astrogliosis in a mouse SCI model. The results suggest that utilizing clinically proven PCSs to deliver NSCs could significantly enhance the efficacy and translational potential of emerging NSC-based SCI therapies.

Practical Implications

Enhanced NSC-based SCI therapies

The study suggests that the efficacy and translational potential of NSC-based SCI therapies could be enhanced by delivering NSCs via scaffolds derived from clinically proven PCS.

Clinical Translation

Due to the use of FDA-approved scaffolds, the research facilitates the clinical translation of emerging NSC technologies for SCI.

Targeted SCI Treatment

The PCS physicochemical parameters (pore structure, chemical composition, and cross-linking) can be easily tuned to better modulate specific SCI pathophysiological processes.

Study Limitations

1
The study utilized a mouse dorsal column crush model, which may not fully represent the complexity of human SCI, including contusions.
2
Calculating the survival rate of implanted NSCs was not possible due to NSC proliferation and scaffold degradation.
3
Further research is required to trace the nature of the observed NSC-derived Tuj1+ cells and their functional integration with the surrounding spinal cord tissue.

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