Zhang Xuebao, Zeng Yuanshan, Zhang Wei, Wang Junmei, Wu Jinlang, Li Jun
Department of Histology and Embryology, Institute of Spinal Cord Injury, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
J Neurotrauma. 2007 Dec;24(12):1863-77. doi: 10.1089/neu.2007.0334.
Spinal cord transection results in severe neurological sequelae, and to date, there is no effective treatment. Because of the limited capacity for axonal regeneration in the spinal cord, recovery is minimal. Recently, efforts have been made to establish, by grafting neural tissue, a functional relay-station between the severed stumps of the injured cord. Previously, we used co-transplantation of neural stem cells (NSCs) and Schwann cells (SCs) to improve functional recovery of transected spinal cord. However, this effort has been partially impeded by limited neuronal differentiation of transplanted NSCs. To circumvent this problem, we have pre-differentiated NSCs toward neurons in vitro with the application of retinoic acid (RA) prior to cell grafting. Further, we genetically modified SCs to overexpress human neurotrophin-3 (hNT-3). When these cells were co-transplanted into the transected spinal cord of rats, injured animals had partial improvement (both functionally and structurally), including improved Basso, Beattie, and Bresnahan (BBB) scores, increased axonal regeneration/remyelination, and reduced neuronal loss. However, this pre-differentiation of NSCs in vitro only mildly improved neuronal differentiation of NSCs in vivo.
脊髓横断会导致严重的神经后遗症，并且迄今为止，尚无有效的治疗方法。由于脊髓中轴突再生能力有限，恢复程度极小。最近，人们通过移植神经组织，努力在受损脊髓的断端之间建立一个功能性中继站。此前，我们使用神经干细胞（NSCs）和雪旺细胞（SCs）共移植来改善横断脊髓的功能恢复。然而，这一努力因移植的神经干细胞有限的神经元分化而受到部分阻碍。为了规避这个问题，我们在细胞移植前，在体外应用视黄酸（RA）将神经干细胞预分化为神经元。此外，我们对雪旺细胞进行基因改造，使其过度表达人神经营养因子-3（hNT-3）。当将这些细胞共移植到大鼠横断脊髓中时，受伤动物有部分改善（功能和结构上均有改善），包括巴索、贝蒂和布雷斯纳汉（BBB）评分提高、轴突再生/髓鞘再生增加以及神经元损失减少。然而，神经干细胞在体外的这种预分化仅轻微改善了其在体内的神经元分化。
