Regrowth of axons into the distal spinal cord through a Schwann‐cell‐seeded mini‐channel implanted into hemisected adult rat spinal cord

Abstract

Schwann cells (SCs) have been shown to be a key element in promoting axonal regeneration after being grafted into the central nervous system (CNS). In the present study, SC-supported axonal regrowth was tested in an adult rat spinal cord implantation model. This model is characterized by a right spinal cord hemisection at the eighth thoracic segment, implantation of a SC-containing mini-channel and restoration of cerebrospinal fluid circulation by suturing the dura. We demonstrate that a tissue cable containing grafted SCs formed an effective bridge between the two stumps of the hemicord 1 month after transplantation. Approximately 10 000 myelinated and unmyelinated axons (1 : 9) per cable were found at its midpoint. In addition to propriospinal axons and axons of peripheral nervous system (PNS) origin, axons from as many as 19 brainstem regions also grew into the graft without additional treatments. Most significantly, some regenerating axons in the SC grafts were able to penetrate through the distal graft-host interface to re-enter the host environment, as demonstrated by anterograde axonal labelling. These axons coursed toward, and then entered the grey matter where terminal bouton-like structures were observed. In channels containing no SCs, limited axonal growth was seen within the graft and no axons penetrated the distal interface. These findings further support the notion that SCs are strong promotors of axonal regeneration and that the mini-channel model may be appropriate for further investigation of axonal re-entry, synaptic reconnection and functional recovery following spinal cord injury.

Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells

“…Furthermore, preservation of even a small percentage of tissue significantly enhances functional recovery (7). Although there have been encouraging reports of deficit reduction (8)(9)(10) and axonal regrowth by blocking inhibitory molecules and antagonizing secondary injury mechanisms (11); myelin replacement by stem (12), Schwann (13), and olfactory ensheathing cells (14,15); delivery of growth factors (16)(17)(18) and small molecules (19); and implantation of fetal tissue (19) and scaffolds (20)(21)(22)(23), as yet there is no practical treatment for SCI.…”

Peripheral Nerve Grafts and Chondroitinase ABC Application Improves Functional Recovery After Complete Spinal Cord Transection

“…This creates an anatomical gap that axons are unable to cross. There have been several approaches used to bridge this anatomical gap, including poly(lactide-co-glycolide) (PLGA) scaffolds [9,10], Schwann cells [11], poly(ethylene glycol) hydrogels [12,13], agarose scaffolds [14,15], and peripheral nerve grafts (PNGs) [16][17][18][19][20][21][22]. PNGs are a living tissue containing several growth factors that have been shown to promote axonal growth, and cytokines that modulate inflammation [23,24].…”

Biodegradable Cell-Seeded Nanofiber Scaffolds for Neural Repair

“…Xu et al studied the efficacy of using a Schwann cell-seeded PAN/polyvinyl chloride (PVC) mini-channel on repairing a hemisected adult rat spinal cord [205]. One month post-surgery, a tissue cable was observed in Schwann-cell seeded channel with significantly more myelinated axons and blood vessels, and larger cross sectional area than the control group without seeded cells.…”

“…Furthermore, a subpopulation of the regenerated axons was also observed to have penetrated the distal interface and re-entered the grey matter, a phenomenon that did not occur in the control group. Cultured Schwann cells were demonstrated to have survived in the distal host environment and promoted the axonal regrowth [205]. Novikova et al evaluated the influence of a Schwann cell-seeded poly-β-hydroxybutyrate (PHB) conduit with a unidirectional fiber orientation on axonal regeneration after cervical SCI in rats [206].…”