Embryonic radial glia bridge spinal cord lesions and promote functional recovery following spinal cord injury

• Published in: Experimental neurology 2005-06, Vol.193 (2), p.394-410
• Main Authors: Hasegawa, Koichi, Chang, Yu-Wen, Li, Hedong, Berlin, Yana, Ikeda, Osamu, Kane-Goldsmith, Noriko, Grumet, Martin
• Format: Article
• Language: English
• Subjects: Animals; Antigens - metabolism; BBB; Behavior, Animal; Biological and medical sciences; Carrier Proteins - metabolism; Cell Differentiation - physiology; Cells, Cultured; Cerebrospinal fluid. Spinal cord. Spinal roots. Spinal nerves; Chondroitin Sulfates - metabolism; Clone Cells - physiology; Ectodysplasins; Embryo, Mammalian; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Female; Fibroblasts - physiology; Fibroblasts - transplantation; Fluorescent Antibody Technique - methods; Glial Fibrillary Acidic Protein - metabolism; Green Fluorescent Proteins - metabolism; Indoles - metabolism; Injuries of the nervous system and the skull. Diseases due to physical agents; Intermediate Filament Proteins - metabolism; Macrophages; Male; Medical sciences; Membrane Proteins - metabolism; Motor Activity - physiology; Nerve Tissue Proteins - metabolism; Nestin; Neurofilament Proteins - metabolism; Neurofilaments; Neuroglia - cytology; Neuron–glia interaction; Neuroprotection; Neurosurgery; Prosencephalon - cytology; Prosencephalon - embryology; Proteoglycans; Proteoglycans - metabolism; Radial glial cells; Rats; Rats, Sprague-Dawley; Recovery of Function - physiology; Spinal Cord Injuries - surgery; Stem Cell Transplantation; Stem Cells - physiology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Time Factors; Traumas. Diseases due to physical agents; Tubulin - metabolism
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2004.12.024

Radial glial cells are neural stem cells (NSC) that are transiently found in the developing CNS. To study radial glia, we isolated clones following immortalization of E13.5 GFP rat neurospheres with v-myc. Clone RG3.6 exhibits polarized morphology and expresses the radial glial markers nestin and brain lipid binding protein. Both NSC and RG3.6 cells migrated extensively in the adult spinal cord. However, RG3.6 cells differentiated into astroglia slower than NSC, suggesting that immortalization can delay differentiation of radial glia. Following spinal cord contusion, implanted RG3.6 cells migrated widely in the contusion site and into spared white matter where they exhibited a highly polarized morphology. When injected immediately after injury, RG3.6 cells formed cellular bridges surrounding spinal cord lesion sites and extending into spared white matter regions in contrast to GFP fibroblasts that remained in the lesion site. Behavioral analysis indicated higher BBB scores in rats injected with RG3.6 cells than rats injected with fibroblasts or medium as early as 1 week after injury. Spinal cords transplanted with RG3.6 cells or dermal fibroblasts exhibited little accumulation of chondroitin sulfate proteoglycans (CSPG) including NG2 proteoglycans that are known to inhibit axonal growth. Reduced levels of CSPG were accompanied by little accumulation in the injury site of activated macrophages, which are a major source of CSPG. However, increased staining and organization of neurofilaments were found in injured rats transplanted with RG3.6 cells suggesting neuroprotection or regrowth. The combined results indicate that acutely transplanted radial glia can migrate to form bridges across spinal cord lesions in vivo and promote functional recovery following spinal cord injury by protecting against macrophages and secondary damage.