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用于神经创伤的内源性和外源性中枢神经系统衍生的干细胞/祖细胞方法。

Endogenous and exogenous CNS derived stem/progenitor cell approaches for neurotrauma.

作者信息

Kulbatski I, Mothe A J, Nomura H, Tator C H

机构信息

Toronto Western Hospital, 399 Bathurst Street McLaughlin Pavilion #12-423, Toronto, Ontario, M5T-2S8, Canada.

出版信息

Curr Drug Targets. 2005 Feb;6(1):111-26. doi: 10.2174/1389450053345037.

Abstract

Neural stem/progenitor cells capable of generating new neurons and glia, reside in specific areas of the adult mammalian central nervous system (CNS), including the ependymal region of the spinal cord and the subventricular zone (SVZ), hippocampus, and dentate gyrus of the brain. Much is known about the neurogenic regions in the CNS, and their response to various stimuli including injury, neurotrophins (NFs), morphogens, and environmental factors like learning, stress, and aging. This work has shaped our current views about the CNS's potential to recover lost tissue and function post-traumatically and the therapies to support the intrinsic regenerative capacity of the brain or spinal cord. Recently, intensive research has explored the potential of harvesting, culturing, and transplanting neural stem/progenitors as a therapeutic intervention for spinal cord injury (SCI) and traumatic brain injury (TBI). Another strategy has focused on maximizing the potential of this endogenous population of cells by stimulating their recruitment, proliferation, migration, and differentiation in vivo following traumatic lesions to the CNS. The promise of such experimental treatments has prompted tissue and biomaterial engineers to implant synthetic three-dimensional biodegradable scaffolds seeded with neural stem/progenitors into CNS lesions. Although there is no definitive answer about the ideal cell type for transplantation, strong evidence supports the use of region specific neural stem/progenitors. The technical and logistic considerations for transplanting neural stem/progenitors are extensive and crucial to optimizing and maintaining cell survival both before and after transplantation, as well as for tracking the fate of transplanted cells. These issues have been systematically addressed in many animal models, that has improved our understanding and approach to clinical therapeutic paradigms.

摘要

能够生成新的神经元和神经胶质细胞的神经干细胞/祖细胞,存在于成年哺乳动物中枢神经系统(CNS)的特定区域,包括脊髓的室管膜区域、脑室下区(SVZ)、海马体以及大脑的齿状回。人们对中枢神经系统中的神经发生区域及其对各种刺激的反应了解很多,这些刺激包括损伤、神经营养因子(NFs)、形态发生素以及学习、压力和衰老等环境因素。这项工作塑造了我们目前对于中枢神经系统在创伤后恢复受损组织和功能的潜力以及支持大脑或脊髓内在再生能力的疗法的看法。最近,深入的研究探索了采集、培养和移植神经干细胞/祖细胞作为脊髓损伤(SCI)和创伤性脑损伤(TBI)治疗干预手段的潜力。另一种策略则专注于通过刺激中枢神经系统创伤性损伤后体内这些内源性细胞群体的募集、增殖、迁移和分化,来最大化它们的潜力。此类实验性治疗的前景促使组织和生物材料工程师将接种了神经干细胞/祖细胞的合成三维可生物降解支架植入中枢神经系统损伤部位。尽管对于理想的移植细胞类型尚无定论,但有力证据支持使用区域特异性神经干细胞/祖细胞。移植神经干细胞/祖细胞的技术和后勤方面的考虑非常广泛,对于优化和维持移植前后细胞的存活以及追踪移植细胞的命运至关重要。在许多动物模型中已经系统地解决了这些问题,这增进了我们对临床治疗模式的理解和方法。

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