Nakamura M, Okano H, Toyama Y, Dai H N, Finn T P, Bregman B S
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.
J Neurosci Res. 2005 Aug 15;81(4):457-68. doi: 10.1002/jnr.20580.
Great interest exists in using cell replacement strategies to repair the damaged central nervous system. Previous studies have shown that grafting rat fetal spinal cord into neonate or adult animals after spinal cord injury leads to improved anatomic growth/plasticity and functional recovery. It is clear that fetal tissue transplants serve as a scaffold for host axon growth. In addition, embryonic Day 14 (E14) spinal cord tissue transplants are also a rich source of neural-restricted and glial-restricted progenitors. To evaluate the potential of E14 spinal cord progenitor cells, we used in vitro-expanded neurospheres derived from embryonic rat spinal cord and showed that these cells grafted into lesioned neonatal rat spinal cord can survive, migrate, and differentiate into neurons and oligodendrocytes, but rarely into astrocytes. Synapses and partially myelinated axons were detected within the transplant lesion area. Transplanted progenitor cells resulted in increased plasticity or regeneration of corticospinal and brainstem-spinal fibers as determined by anterograde and retrograde labeling. Furthermore, transplantation of these cells promoted functional recovery of locomotion and reflex responses. These data demonstrate that progenitor cells when transplanted into neonates can function in a similar capacity as transplants of solid fetal spinal cord tissue.
人们对使用细胞替代策略修复受损的中枢神经系统有着浓厚的兴趣。先前的研究表明，脊髓损伤后将大鼠胎儿脊髓移植到新生或成年动物体内可改善解剖学上的生长/可塑性和功能恢复。很明显，胎儿组织移植可作为宿主轴突生长的支架。此外，胚胎第14天（E14）脊髓组织移植也是神经限制和胶质限制祖细胞的丰富来源。为了评估E14脊髓祖细胞的潜力，我们使用了从胚胎大鼠脊髓体外扩增的神经球，并表明这些移植到新生大鼠脊髓损伤部位的细胞能够存活、迁移并分化为神经元和少突胶质细胞，但很少分化为星形胶质细胞。在移植损伤区域内检测到了突触和部分髓鞘化的轴突。通过顺行和逆行标记确定，移植的祖细胞导致皮质脊髓和脑干脊髓纤维的可塑性或再生增加。此外，这些细胞的移植促进了运动和反射反应的功能恢复。这些数据表明，祖细胞移植到新生动物体内时，其功能与实体胎儿脊髓组织移植相似。
