Lee Kyung Hee, Yoon Do Heum, Park Yong Gou, Lee Bae Hwan
Medical Research Center, Yonsei University College of Medicine, Seoul, Korea.
J Neurotrauma. 2005 May;22(5):575-89. doi: 10.1089/neu.2005.22.575.
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.
为了使脊髓损伤(SCI)的治疗效果最大化,人们已经做出了许多努力。最近,有报道称少突胶质细胞2型星形胶质细胞(O-2A)祖细胞可使成年大鼠脱髓鞘脊髓的局部区域重新髓鞘化。我们进行了一项研究,以调查在急性脊髓损伤大鼠模型中移植O-2A细胞的治疗潜力。在大鼠的T9节段用纽约大学冲击器诱导脊髓损伤。在脊髓损伤诱导后1周,将用溴脱氧尿苷(BrdU)标记的O-2A细胞移植到脊髓损伤部位。细胞移植后6周,行为测试显示,与仅给予细胞培养基的动物相比,接受O-2A细胞移植的动物功能有显著改善。电生理研究表明,移植并没有改善体感诱发电位的幅度或潜伏期,但运动诱发电位记录显示,O-2A细胞移植组这些电位的潜伏期明显短于细胞培养基治疗组。在移植BrdU标记的O-2A细胞后,在脊髓损伤部位及其附近检测到BrdU阳性细胞。还检测到同时标记有BrdU和2',3'-环核苷酸-3-磷酸二酯酶的细胞,表明移植的O-2A细胞分化为少突胶质细胞。相比之下,未检测到标记有BrdU和胶质纤维酸性蛋白或神经元核抗原的细胞。此外,束路追踪研究表明,O-2A细胞移植后脑干区域逆行标记神经元的数量增加。研究数据表明,O-2A细胞移植到脊髓损伤动物体内后,迁移到损伤部位附近区域并分化为少突胶质细胞。行为测试以及电生理和形态学研究表明,O-2A细胞移植可能在脊髓损伤后的功能恢复和轴突再生中发挥重要作用。