Schwann Cell Transplantation and Descending Propriospinal Regeneration after Spinal Cord Injury

Brain Res, 2015 · DOI: 10.1016/j.brainres.2014.09.038 · Published: September 4, 2015

Spinal Cord Injury Neurology Regenerative Medicine & Stem Cells

Simple Explanation

After a spinal cord injury (SCI), the damaged nerve fibers in the central nervous system (CNS) have a limited ability to regrow, resulting in minimal functional recovery. Schwann cells (SCs) are a promising treatment option for promoting nerve fiber regrowth in the CNS, including the spinal cord. Compared to other nerve pathways in the CNS, the propriospinal tracts show the best regrowth response when SCs are transplanted. These nerve fibers can grow into the SC environment even without extra growth factors, which is uncommon in other CNS tracts. Since SCs secrete several important growth factors that the propriospinal tract responds to, SCs are considered one of the most promising cell-based therapies for SCI. This review specifically focuses on using SC transplantation to help descending propriospinal axons regrow and how to improve this regrowth with various combined strategies.

Study Duration

Not specified

Participants

Animal models of SCI

Evidence Level

Review

Key Findings

1
Propriospinal tracts (PSTs) possess greater innate regenerative capacity, and have been shown to strongly respond to PN/SC grafts.
2
The plasticity of CST axons that innervate dPST neurons and subsequent regeneration of dPST axons beyond the lesion site may provide an alternative pathway or “functional relay” for transmission of supraspinal motor command down to the spinal cord to promote motor recovery.
3
Acute or sub-acute phase (one or two weeks after injury) is the optimal time window for the treatment of the propriospinal axonal regeneration.

Research Summary

The propriospinal system is important for normal spinal cord physiology as well as functional recovery after SCI in all mammals. Propriospinal neurons are the most promising targets for therapeutic interventions after SCI compared to neurons originated from other CNS regions such as in the sensorimotor cortex and the red nucleus. To promote a complete functional regeneration, several critical steps have been proposed which may include (i) enhancing the intrinsic regenerative capacity of injured neurons, (ii) manipulating the interaction between the grafted SCs and host astrocytes making the graft-host interface more permissive for axon growth, and (iii) reducing or removing inhibitory molecules associated with the glial scar.

Practical Implications

Improved SCI Therapies

Focusing on propriospinal neuron regeneration through SC transplantation could lead to more effective treatments for SCI.

Optimal Timing of Intervention

Administering therapies in the acute or sub-acute phase post-injury can maximize propriospinal axonal regeneration.

Combination Therapies

Combining SC transplantation with neurotrophic factors and glial scar modification enhances axonal regeneration and functional recovery.

Study Limitations

1
Limited regeneration beyond the graft environment.
2
Disorderly axonal regeneration along the rostral-caudal orientation under transplantation interference.
3
Efficiency of regenerated synapses in transducing information may not be optimal.

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