Graft of a Tissue-Engineered Neural Scaffold Serves as a Promising Strategy to Restore Myelination after Rat Spinal Cord Transection

Abstract

Remyelination remains a challenging issue in spinal cord injury (SCI). In the present study, we cocultured Schwann cells (SCs) and neural stem cells (NSCs) with overexpression of neurotrophin-3 (NT-3) and its high affinity receptor tyrosine kinase receptor type 3 (TrkC), respectively, in a gelatin sponge (GS) scaffold. This was aimed to generate a tissue-engineered neural scaffold and to investigate whether it could enhance myelination after a complete T10 spinal cord transection in adult rats. Indeed, many NT-3 overexpressing SCs (NT-3-SCs) in the GS scaffold assumed the formation of myelin. More strikingly, a higher incidence of NSCs overexpressing TrkC differentiating toward myelinating cells was induced by NT-3-SCs. By transmission electron microscopy, the myelin sheath showed distinct multilayered lamellae formed by the seeded cells. Eighth week after the scaffold was transplanted, some myelin basic protein (MBP)-positive processes were observed within the transplantation area. Remarkably, certain segments of myelin derived from NSC-derived myelinating cells and NT-3-SCs were found to ensheath axons. In conclusion, we show here that transplantation of the GS scaffold promotes exogenous NSC-derived myelinating cells and SCs to form myelins in the injury/transplantation area of spinal cord. These findings thus provide a neurohistological basis for the future application or transplantation using GS neural scaffold to repair SCI.

Complete rat spinal cord transection as a faithful model of spinal cord injury for translational cell transplantation

“…The major flaw of complete section is high severity of the injury reflected in slightly elevated mortality rate during the post-trasplantation period comparing to other models with the advantage that any regenerative effect can be attributed exclusively to exogenous treatments. This model together with the hemisection is also very useful to test various “bridging gap” biomaterial or device studies alone or in combination with cell grafts242526272829. Various studies used this model to study the effects of combination of different scaffolds and biomaterials and stem cells on axon regeneration after injury, such as a polymer scaffold with rat bone marrow stem cells3031.…”

A hybrid microfluidic system for regulation of neural differentiation in induced pluripotent stem cells

“…Absence of movement and sensation occurs in spinal cord injury (SCI) below the level of the injured spinal cord. To date, no efficient treatment has taken place to completely repair SCI . Recently, transplantation of stem and progenitor cells incorporating various types of scaffolds to the injury sites has shown auspicious results for SCI therapy …”

Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

“…A variable number of nerve fibers were unmyelinated. Remyelination has been reported in a separate SCI study using NT‐3 overexpressing transgenic Schwann cells 40. A study using LINGO‐1 antagonist showed the presence of many new myelin in lumbar spinal cord of rats41 suggesting therefore that formation of multiple layered myelin sheath in hemisected SCI canine is possible.…”