Genetic Manipulation of Neural Stem Cells for Transplantation into the Injured Spinal Cord

Cellular and Molecular Neurobiology, 2007 · DOI: 10.1007/s10571-006-9119-8 · Published: December 7, 2006

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

The injured spinal cord doesn't naturally regenerate well. Engrafted neural precursor cells often become astroglia instead of neurons or oligodendroglia, which are needed for repair. Scientists are trying to genetically modify these precursor cells to encourage them to become neurons or oligodendroglia. This involves using genes like noggin or neurogenic transcription factors. These genetic manipulations have shown interesting results, offering potential for improving cell-based therapies for spinal cord injuries.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
Transplantation of ES cell-derived oligodendrocyte progenitor cells (OPCs) into contusion-injured adult rat spinal cord OPCs can differentiate into oligodendrocytes and improve locomotor ability if transplanted early after injury.
2
Noggin-expressing NPCs generated more neuron-like cells and oligodendroglia compared to control NPCs in neurosphere cultures, correlating with additional functional recovery.
3
Neurogenin-2 expressing NPCs increased myelination at the injury site, and significantly improved locomotor function and sensory responses compared to control.

Research Summary

The injured adult spinal cord is not conducive for neuronal regeneration and neurogenesis. Engrafted neural precursor cells (NPCs) differentiate largely into astroglia, with only a very small percentage becoming neurons or oligodendroglia. Several recent attempts have been made to enhanced neurogenesis or oligodendroglia differentiation of transplanted NPCs by genetic manipulation.

Practical Implications

Enhanced Remyelination

Transplantation of manipulated neural stem cells may promote remyelination of demyelinated neurons in spinal cord injuries.

Functional Recovery

Genetic manipulation of NPCs could lead to improved locomotor function and sensory responses after spinal cord injury.

Reduced Allodynia

Specific genetic modifications, such as Neurogenin-2 expression, might reduce allodynia (hypersensitivity) in spinal cord injury patients.

Study Limitations

1
The adult spinal cord appeared to allow neuronal dif- ferentiation of lineage-restricted neural precursors into neurons, the injured spinal cord appears to harbor a pathological microenvironment that in-hibits neuronal differentiation
2
Direct evidence for functional integration of differentiated neurons is sorely lacking.
3
The pathophysiological microenvironment of the injured spinal cord of NOD-scid mice may not be similar to human injured spinal cords

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