Blits Bas, Boer Gerard J, Verhaagen Joost
Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research.
Cell Transplant. 2002;11(6):593-613.
In this review, recent studies using pharmacological treatment, cell transplantation, and gene therapy to promote regeneration of the injured spinal cord in animal models will be summarized. Pharmacological and cell transplantation treatments generally revealed some degree of effect on the regeneration of the injured ascending and descending tracts, but further improvements to achieve a more significant functional recovery are necessary. The use of gene therapy to promote repair of the injured nervous system is a relatively new concept. It is based on the development of methods for delivering therapeutic genes to neurons, glia cells, or nonneural cells. Direct in vivo gene transfer or gene transfer in combination with (neuro)transplantation (ex vivo gene transfer) appeared powerful strategies to promote neuronal survival and axonal regrowth following traumatic injury to the central nervous system. Recent advances in understanding the cellular and molecular mechanisms that govern neuronal survival and neurite outgrowth have enabled the design of experiments aimed at viral vector-mediated transfer of genes encoding neurotrophic factors, growth-associated proteins, cell adhesion molecules, and antiapoptotic genes. Central to the success of these approaches was the development of efficient, nontoxic vectors for gene delivery and the acquirement of the appropriate (genetically modified) cells for neurotransplantation. Direct gene transfer in the nervous system was first achieved with herpes viral and El-deleted adenoviral vectors. Both vector systems are problematic in that these vectors elicit immunogenic and cytotoxic responses. Adeno-associated viral vectors and lentiviral vectors constitute improved gene delivery systems and are beginning to be applied in neuroregeneration research of the spinal cord. Ex vivo approaches were initially based on the implantation of genetically modified fibroblasts. More recently, transduced Schwann cells, genetically modified pieces of peripheral nerve, and olfactory ensheathing glia have been used as implants into the injured spinal cord.
在本综述中，将总结近期在动物模型中使用药物治疗、细胞移植和基因治疗促进脊髓损伤再生的研究。药物和细胞移植治疗通常对损伤的上下行神经束再生显示出一定程度的效果，但仍需进一步改进以实现更显著的功能恢复。利用基因治疗促进受损神经系统的修复是一个相对较新的概念。它基于将治疗性基因传递给神经元、神经胶质细胞或非神经细胞的方法的发展。直接体内基因转移或基因转移与（神经）移植相结合（体外基因转移）似乎是促进中枢神经系统创伤性损伤后神经元存活和轴突再生的有效策略。在理解控制神经元存活和神经突生长的细胞和分子机制方面的最新进展，使得能够设计旨在通过病毒载体介导转移编码神经营养因子、生长相关蛋白、细胞粘附分子和抗凋亡基因的实验。这些方法成功的关键在于开发高效、无毒的基因传递载体以及获得用于神经移植的合适（基因修饰）细胞。神经系统中的直接基因转移最初是通过疱疹病毒和E1缺失腺病毒载体实现的。这两种载体系统都存在问题，因为这些载体引发免疫原性和细胞毒性反应。腺相关病毒载体和慢病毒载体构成了改进的基因传递系统，并开始应用于脊髓神经再生研究。体外方法最初基于植入基因修饰的成纤维细胞。最近，转导的雪旺细胞、基因修饰的周围神经片段和嗅鞘胶质细胞已被用作植入受损脊髓的移植物。
