Astrocyte progenitor transplantation promotes regeneration of bulbospinal respiratory axons, recovery of diaphragm function, and a reduced macrophage response following cervical spinal cord injury

Glia, 2019 · DOI: 10.1002/glia.23555 · Published: March 1, 2019

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study explores a new way to treat spinal cord injury by transplanting special cells, called astrocyte progenitors, into the injured spinal cord. These cells can turn into astrocytes, a type of brain cell that can help damaged nerve fibers regrow. The researchers found that transplanting these astrocyte progenitors helped rats with spinal cord injuries regain some breathing function. The transplanted cells also encouraged damaged nerve fibers to regrow and reduced inflammation in the injured area. The findings suggest that using astrocyte progenitor transplantation could be a helpful way to improve breathing and nerve regeneration after spinal cord injury, potentially offering a new approach to treating this condition.

Study Duration

5 weeks

Participants

Sprague–Dawley rats (n = 7-9 per group)

Evidence Level

Not specified

Key Findings

1
GRP transplantation promoted significant recovery of diaphragm electromyography amplitudes, demonstrating substantial recovery of diaphragm function.
2
GRPs stimulated robust regeneration of injured rVRG axons but no synaptic reconnection of these regrowing fibers with PhMNs.
3
GRPs significantly reduced the macrophage response both within the lesion site and in the intact caudal spinal cord surrounding PhMNs.

Research Summary

Intraspinal transplantation of astrocyte progenitors in the C2 hemisection model of SCI promoted: (a) significant recovery of diaphragmatic respiratory function, (b) robust regeneration of damaged bulbospinal rVRG axons, (c) extensive sprouting of both spared contralateral rVRG axons and 5-HT fibers, and (d) a pronounced reduction in the axonal growth-inhibitory macrophage response both in the lesion site and surrounding PhMNs in the intact spinal cord distal to the lesion. We showed that GRP transplantation induced regeneration of injured ipsilateral rVRG axons into and across the lesion site; however, these axons did not re-enter intact spinal cord distal to the hemisection site. We also demonstrated that GRPs stimulated extensive sprouting of spared contralateral rVRG axons and 5-HT axons within the ventral horn ipsilateral/caudal to the hemisection, suggesting that the generation of alternative circuits may be responsible for functional improvement.

Practical Implications

Therapeutic potential

Transplantation-based delivery of astrocytes to the injured spinal cord is a promising approach for promoting respiratory recovery.

Plasticity mechanisms

Astrocyte progenitor transplants can promote plasticity in injured and spared neural circuits following SCI.

Clinical relevance

The results are relevant to diaphragm function but also to the host of other circuits and functional outcomes disrupted by spinal cord trauma.

Study Limitations

1
Regenerating rVRG fibers did not reinnervate PhMNs as no rVRG axons crossed the caudal lesion–intact interface to re-enter distal spinal cord
2
The beneficial effects of GRPs on the macrophage response was most pronounced within the lesion
3
Analysis of axonal growth and macrophage response following GRP injection was conducted at a single late time point post-injury

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