Fernandez Eduardo, Mannino Stefano, Tufo Tommaso, Pallini Roberto, Lauretti Liverana, Albanese Alessio, Denaro Luca
Department of Neurosurgery, Center of Research on Regeneration in the Nervous System, Catholic University School of Medicine, 00168 Rome, Italy.
Surg Neurol. 2006 Mar;65(3):223-37. doi: 10.1016/j.surneu.2005.06.039.
Spinal cord injury often results in irreversible and permanent neurologic deficits below the lesion level. Nowadays, treatment is limited to drugs and/or physiotherapy aimed at compensating disability. New experimental studies focus on the transplantation of cells capable of surviving, regenerating tissue, recovering functions and/or improving symptoms. A review of such type of studies on spinal cord reconstruction published between 1991 and 2004 is presented. In the latter years, cell transplantation appeared as the most promising approach in spinal cord regeneration research. To date, this promise has not been maintained, despite the appearance of new attractive cell populations for grafting, such as neural stem cells. The demonstration that stem cells exist in the adult brain and that they can be isolated and expanded in vitro offers the possibility to test such interesting cells in the paraplegic rat. Some neurotrophic factors can facilitate axonal regeneration and neuronal survival. Therefore, the development of strategies, such as implanting neural stem cells engineered to secrete neurotrophic factors directly in the lesion site, could be important to promote regeneration in the injured spinal cord. Despite all the strategies used till now, the problem of the paraplegic rat remains. Only the solution of such problem will authorize studies in higher mammals and, finally, the clinical application in human patients. The paraplegic adult rat with a T8 spinal cord transection should be considered the standard experimental model to be used in spinal cord reconstruction studies. Function and anatomic results are undisputed only after spinal cord transection.
脊髓损伤常导致损伤平面以下出现不可逆的永久性神经功能缺损。如今,治疗方法仅限于旨在补偿残疾的药物和/或物理治疗。新的实验研究聚焦于移植能够存活、再生组织、恢复功能和/或改善症状的细胞。本文对1991年至2004年间发表的此类脊髓重建研究进行了综述。近年来,细胞移植在脊髓再生研究中似乎是最具前景的方法。然而,尽管出现了如神经干细胞等新的有吸引力的移植细胞群体,但迄今为止,这一前景并未得到维持。成体脑中存在干细胞且可在体外分离和扩增这一事实,为在截瘫大鼠中测试此类有趣的细胞提供了可能性。一些神经营养因子可促进轴突再生和神经元存活。因此,开发诸如将经过基因工程改造以分泌神经营养因子的神经干细胞直接植入损伤部位等策略,对于促进损伤脊髓的再生可能具有重要意义。尽管到目前为止已采用了所有策略,但截瘫大鼠的问题依然存在。只有解决了这一问题,才能够开展对高等哺乳动物的研究,并最终应用于人类患者的临床治疗。成年T8脊髓横断的截瘫大鼠应被视为脊髓重建研究中使用的标准实验模型。只有在脊髓横断后,功能和解剖学结果才无可争议。