Effects of glial transplantation on functional recovery following acute spinal cord injury.
Numerous efforts have been made to maximize the efficacy of treatment for spinal cord injury (SCI). Recently, oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells have been reported to remyelinate focal areas of demyelinated spinal cord in adult rats. We conducted a study to investigate the therapeutic potential of transplantation of O-2A cells in a rat model of acute SCI. SCI was induced with an NYU Impactor at T9 of rats. O-2A cells labeled with bromodeoxyuridine (BrdU) were transplanted into sites of SCI at 1 week after the induction of SCI. At 6 weeks after cell transplantation, a behavioral test showed significant functional improvement in animals that had received O-2A-cell transplants as compared to animals given cell-culture medium alone. An electrophysiological study revealed that the transplants did not improve the amplitude or latency of somatosensory evoked potentials, but a recording of motor evoked potentials showed that the latency of these potentials in the O-2A-cell-transplant group was significantly shorter than that in the group treated with cell-culture medium. Following transplantation of BrdU-labeled O-2A cells, cells positive for BrdU were detected at and near sites of SCI. Cells labeled for both BrdU and 2',3' -cyclic nucleotide-3-phosphodiesterase were also detected, showing that the transplanted O-2A cells differentiated into oligodendrocytes. By contrast, cells labeled for BrdU and glial fibrillary acidic protein, or for neuronal nuclei antigen, were not detected. Furthermore, a tract-tracing study showed that numbers of retrogradely labeled neurons increased in areas of the brain stem after O-2A-cell transplantation. The study data showed that after being transplanted into an animal with SCI, O-2A cells migrated to the area adjacent to the site of injury and differentiated into oligodendrocytes. The behavioral test and the electrophysiological and morphological studies showed that transplantation of O-2A cells may play an important role in functional recovery and the regeneration of axons after SCI.
Lee
Kyung Hee
KH
Medical Research Center, Yonsei University College of Medicine, Seoul, Korea.
Yoon
Do Heum
DH
Park
Yong Gou
YG
Lee
Bae Hwan
BH
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D001933:Brain Stem / Q000166:cytology / Q000502:physiology; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000166:cytology / Q000502:physiology; D005456:Fluorescent Dyes; D006085:Graft Survival / Q000502:physiology; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D009473:Neuronal Plasticity / Q000502:physiology; D009836:Oligodendroglia / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D016896:Treatment Outcome
D005456:Fluorescent Dyes; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D001973:Bromodeoxyuridine