title: Platelet-derived growth factor-responsive neural precursors give rise to myelinating oligodendrocytes after transplantation into the spinal cords of contused rats and dysmyelinated mice.
abstract: Spinal cord injury (SCI) results in substantial oligodendrocyte death and subsequent demyelination leading to white-matter defects. Cell replacement strategies to promote remyelination are under intense investigation; however, the optimal cell for transplantation remains to be determined. We previously isolated a platelet-derived growth factor (PDGF)-responsive neural precursor (PRP) from the ventral forebrain of fetal mice that primarily generates oligodendrocytes, but also astrocytes and neurons. Importantly, human PRPs were found to possess a greater capacity for oligodendrogenesis than human epidermal growth factor- and/or fibroblast growth factor-responsive neural stem cells. Therefore, we tested the potential of PRPs isolated from green fluorescent protein (GFP)-expressing transgenic mice to remyelinate axons in the injured rat spinal cord. PRPs were transplanted 1 week after a moderate thoracic (T9) spinal cord contusion in adult male rats. After initial losses, PRP numbers remained stable from 2 weeks posttransplantation onward and those surviving cells integrated into host tissue. Approximately one-third of the surviving cells developed the typical branched phenotype of mature oligodendrocytes, expressing the marker APC-CC1. The close association of GFP cells with myelin basic protein as well as with Kv1.2 and Caspr in the paranodal and juxtaparanodal regions of nodes of Ranvier indicated that the transplanted cells successfully formed mature myelin sheaths. Transplantation of PRPs into dysmyelinated Shiverer mice confirmed the ability of PRP-derived cells to produce compact myelin sheaths with normal periodicity. These findings indicate that PRPs are a novel candidate for CNS myelin repair, although PRP-derived myelinating oligodendrocytes were insufficient to produce behavioral improvements in our model of SCI.
authors.affiliation: International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Plemel
authors.forename: Andrew
authors.initials: A
authors.lastname: Chojnacki
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Sparling
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Ward
authors.initials: W
authors.lastname: Plunet
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Duncan
authors.forename: So Eyun
authors.initials: SE
authors.lastname: Park
authors.forename: Samuel
authors.initials: S
authors.lastname: Weiss
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tetzlaff
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D010982:Platelet-Derived Growth Factor