Embryonic radial glia bridge spinal cord lesions and promote functional recovery following spinal cord injury.
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.
Hasegawa
Koichi
K
W. M. Keck Center for Collaborative Neuroscience, 604 Allison Road, Rutgers, State University of New Jersey, Piscataway, NJ 08854-8082, USA.
Chang
Yu-Wen
YW
Li
Hedong
H
Berlin
Yana
Y
Ikeda
Osamu
O
Kane-Goldsmith
Noriko
N
Grumet
Martin
M
D000818:Animals; D000941:Antigens / Q000378:metabolism; D001522:Behavior, Animal; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism; D002999:Clone Cells / Q000502:physiology; D053331:Ectodysplasins; D004622:Embryo, Mammalian; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D005347:Fibroblasts / Q000502:physiology / Q000637:transplantation; D005455:Fluorescent Antibody Technique / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology*; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000601:surgery*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D002352:Carrier Proteins; D002809:Chondroitin Sulfates; D053331:Ectodysplasins; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D007211:Indoles; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D016900:Neurofilament Proteins; D011509:Proteoglycans; D014404:Tubulin; D000099216:Chondroitin Sulfate Proteoglycan 4; C490174:Fabp7 protein, rat; C577486:Nes protein, rat; C007293:DAPI