Trueman R C, Klein A, Lindgren H S, Lelos M J, Dunnett S B
School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK.
Curr Top Behav Neurosci. 2013;15:357-98. doi: 10.1007/7854_2012_223.
Restoration of the damaged central nervous system is a vast challenge. However, there is a great need for research into this topic, due to the prevalence of central nervous system disorders and the devastating impact they have on people's lives. A number of strategies are being examined to achieve this goal, including cell replacement therapy, enhancement of endogenous plasticity and the recruitment of endogenous neurogenesis. The current chapter reviews this topic within the context of Parkinson's disease, Huntington's disease and stroke. For each disease exogenous cell therapies are discussed including primary (foetal) cell transplants, neural stem cells, induced pluripotent stem cells and marrow stromal cells. This chapter highlights the different mechanistic approaches of cell replacement therapy versus cells that deliver neurotropic factors, or enhance the endogenous production of these factors. Evidence of exogenously transplanted cells functionally integrating into the host brain, replacing cells, and having a behavioural benefit are discussed, along with the ability of some cell sources to stimulate endogenous neuroprotective and restorative events. Alongside exogenous cell therapy, the role of endogenous neurogenesis in each of the three diseases is outlined and methods to enhance this phenomenon are discussed.
修复受损的中枢神经系统是一项巨大的挑战。然而，鉴于中枢神经系统疾病的普遍性及其对人们生活造成的毁灭性影响，对这一主题的研究需求巨大。目前正在研究多种策略来实现这一目标，包括细胞替代疗法、增强内源性可塑性以及促进内源性神经发生。本章将在帕金森病、亨廷顿病和中风的背景下对这一主题进行综述。针对每种疾病，将讨论外源性细胞疗法，包括原代（胎儿）细胞移植、神经干细胞、诱导多能干细胞和骨髓基质细胞。本章重点介绍了细胞替代疗法与递送神经营养因子或增强这些因子内源性产生的细胞的不同作用机制。讨论了外源性移植细胞在功能上整合到宿主大脑、替代细胞并产生行为益处的证据，以及一些细胞来源刺激内源性神经保护和修复事件的能力。除了外源性细胞疗法，还概述了内源性神经发生在这三种疾病中的作用，并讨论了增强这一现象的方法。
