Platelet-derived growth factor-responsive neural precursors give rise to myelinating oligodendrocytes after transplantation into the spinal cords of contused rats and dysmyelinated mice

• Published in: Glia 2011-12, Vol.59 (12), p.1891-1910
• Main Authors: Plemel, Jason R., Chojnacki, Andrew, Sparling, Joseph S., Liu, Jie, Plunet, Ward, Duncan, Greg J., Park, So Eyun, Weiss, Samuel, Tetzlaff, Wolfram
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Astrocytes; Axons; Central nervous system; Demyelinating Diseases - metabolism; Demyelinating Diseases - pathology; Demyelinating Diseases - surgery; Demyelination; Disease Models, Animal; Female; Forebrain; Green fluorescent protein; Male; Mice; Mice, Neurologic Mutants; Mice, Transgenic; Myelin; Myelin basic protein; Neural stem cells; Neural Stem Cells - cytology; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Nodes of Ranvier; oligodendrocyte; Oligodendrocytes; Oligodendroglia - cytology; Oligodendroglia - drug effects; Oligodendroglia - metabolism; Periodicity; Platelet-derived growth factor; Platelet-Derived Growth Factor - physiology; Potassium channels (voltage-gated); Primary Cell Culture; Rats; Rats, Sprague-Dawley; remyelination; Shiverer mice; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Spinal Cord Injuries - surgery; Spinal cord injury; Stem Cell Transplantation - methods; Thorax; Transgenic mice; Transplantation
• ISSN: 0894-1491; 1098-1136; 1098-1136
• DOI: 10.1002/glia.21232

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. © 2011 Wiley‐Liss, Inc.