Human neuroepithelial stem cell regional speciﬁcity enables spinal cord repair through a relay circuit

Nature Communications, 2018 · DOI: 10.1038/s41467-018-05844-8 · Published: August 23, 2018

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This research explores using human neuroepithelial stem cells (NES) from spinal cord tissue to repair spinal cord injuries in mice. The study found that these cells can integrate into the injured spinal cord, extend axons, and help restore some function. The study highlights the importance of matching the type of stem cell to the location of the injury. Spinal cord-derived stem cells worked better in the spinal cord than stem cells from the brain. The scientists also demonstrated that these transplanted stem cells can form a 'relay circuit,' reconnecting damaged neural pathways. This suggests that stem cell therapy could help to bridge the gap created by spinal cord injuries.

Study Duration

8 weeks post-grafting

Participants

Immunodeficient mice, Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Human spinal cord-derived neuroepithelial stem cells (SC-NES) robustly engraft into lesioned immunodeficient mice.
2
Improved functional recovery depends on neural relay function through the grafted neurons and requires matching of neural identity to the anatomical site of injury.
3
SC-NES cells form a functional relay system in the injured spinal cord, reconnecting supraspinal axons with denervated target neurons.

Research Summary

The study demonstrates the successful derivation and characterization of human SC-NES cells as candidates for cell-based therapy in SCI treatment, showing they are highly expandable and retain neurogenic capacity. When transplanted into injured SC, SC-NES cells exhibit excellent integration properties, differentiating into neurons and extending long-distance axons, leading to amelioration of locomotor deficits. The regional identity of NES cells is crucial for graft integration, with SC-NES cells outperforming NCX-NES cells in spinal cord repair, highlighting the importance of anatomical matching for successful connectivity.

Practical Implications

Therapeutic Potential

Human SC-NES cells offer a promising avenue for cell-based therapy in spinal cord injury treatment due to their ability to integrate, differentiate, and extend axons.

Personalized Medicine

The study emphasizes the importance of matching the regional identity of stem cells to the injury site, suggesting a need for personalized cell therapies based on the specific location of spinal cord damage.

Drug Discovery

Identification of key molecular markers associated with successful engraftment (e.g., MTURN, ATCAY, PTN, KAL1, SYT13, SYT4) can aid in screening and optimizing cell populations for transplantation.

Study Limitations

1
The infiltration of collagen and subsequent formation of an impervious fissure within some grafts may have attenuated the behavioral outcome.
2
Further studies are needed to understand guidance of extending axons to appropriate targets and to determine what effect newly generated circuits may have for autonomic and sensory function.
3
Transition of human cell therapy to the clinic will require more systematic investigations.

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