Long-Distance Axonal Growth from Human Induced Pluripotent Stem Cells After Spinal Cord Injury

Neuron, 2014 · DOI: 10.1016/j.neuron.2014.07.014 · Published: August 20, 2014

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Researchers took cells from an 86-year-old man and turned them into neural stem cells. They then implanted these cells into rats with spinal cord injuries. The implanted cells survived, became neurons and glial cells, and grew axons that stretched throughout the rats' central nervous systems. The rat's own nerve cells also grew into the implanted human cells and made connections, suggesting a possible way to repair spinal cord injuries.

Study Duration

3 months

Participants

Adult immunodeficient rats (N=14) and adult SCID mice (N=4)

Evidence Level

Not specified

Key Findings

1
Human iPSC-derived NSCs survived and differentiated into neurons and glia after transplantation into rats with spinal cord injuries.
2
Grafted human cells extended axons over long distances, essentially spanning the entire rat neuraxis from the lumbar spinal cord to the olfactory bulb.
3
Host rat axons penetrated the human iPSC grafts and formed synapses, and human axons formed synapses with rodent neurons.

Research Summary

Human iPSC-derived neural stem cells were grafted into sites of rat spinal cord injury and were found to extend axons over virtually the entire length of the rat central nervous system. These human axons formed synapses onto rodent neurons, and rodent axons penetrated human grafts and expressed pre-synaptic proteins. This extensive axonal extension occurred from cells of an 86 year-old human, suggesting that age does not limit the plasticity of neural stem cells grafted into models of central injury.

Practical Implications

Potential Therapeutic Strategy

The study demonstrates the potential of iPSC-derived neural stem cells for treating spinal cord injuries due to their capacity for extensive axonal growth and connectivity.

Age is Not a Barrier

The findings suggest that age is not a significant barrier to using iPSC-derived cells for neural repair, as cells from an elderly donor exhibited robust axonal growth.

Overcoming Inhibitory Milieu

The study supports the idea that intrinsic neuronal growth mechanisms can overcome the inhibitory environment of the injured adult CNS, paving the way for therapies promoting axonal regeneration.

Study Limitations

1
Collagenous rifts within the grafts may have prevented the formation of neuronal relays across the lesion site, potentially hindering functional recovery.
2
The lack of detectable myelination of human axons in the rat spinal cord could have affected the efficiency of signal transmission and functional outcomes.
3
Only one human iPSC line was tested, and additional lines need to be evaluated to determine the extent to which heterogeneity in donor source and cell preparation methods may influence outcomes.

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