Cell transplantation in Parkinson's disease: problems and perspectives
Cell transplantation in Parkinson's disease: problems and perspectives
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DOI：
10.1097/wco.0b013e32833b1f62
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发表时间：
2010-08-01
影响因子：
4.8
通讯作者：
Brundin, Patrik
中科院分区：
文献类型：
--
作者：
Allan, Laura E.;Petit, Geraldine H.;Brundin, Patrik
综述的目的我们回顾了最近在帕金森病实验模型中使用胚胎组织和干细胞移植进行的实验。我们还强调了为了使细胞疗法在临床上变得有效和安全而仍需应对的挑战。最近的发现以前的临床移植试验的结果在运动恢复方面是不同的。我们讨论了移植是否可以减轻L-3，4-二羟基苯丙氨酸(L-多巴)诱导的运动障碍，并考虑了易患移植物诱发运动障碍的危险因素。此外，我们还介绍了由欧盟资助的一个新的多中心联盟--Transeuro，该联盟计划进行移植试验。干细胞已经成为产生多巴胺能前体的替代来源。我们简要概述了人类胚胎干细胞的使用进展，并主要集中在诱导多能性这一新兴领域。最后，我们介绍了一种令人兴奋的新的直接重编程方法，这种方法涉及成纤维细胞向神经元的转化，而不会诱导多能状态。概述细胞移植的领域已经通过识别易使患者发生移植物诱导的运动障碍的参数和产生多巴胺能神经元的新方法的出现而重新焕发生机。希望Transeuro的临床试验将进一步推动并成为未来使用干细胞来源的神经元进行试验的垫脚石。
Purpose of reviewWe review recent experiments conducted using embryonic tissue and stem cell transplants in experimental models of Parkinson's disease. We also highlight the challenges which remain to be met in order for cell therapy to become clinically effective and safe.Recent findingsThe outcome of previous clinical transplantation trials was variable in terms of motor recovery. We discuss whether transplants can mitigate L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias and consider the risk factors which predispose to graft-induced dyskinesias. In addition, we introduce Transeuro, a new European Union-funded multicenter consortium which plans to perform transplantation trials. Stem cells have emerged as an alternative source for the generation of dopaminergic precursors. We briefly outline progress made in the use of human embryonic stem cells and focus predominantly on the emerging field of induced pluripotency. We conclude by introducing the exciting and novel method of direct reprogramming which involves the conversion of fibroblasts to neurons without inducing a pluripotent state.SummaryThe area of cell transplantation has been revitalized by the identification of parameters which predispose patients to graft-induced dyskinesias and by the emergence of novel methods of generating dopaminergic neurons. Hopefully, the Transeuro clinical trials will give further impetus and act as a stepping stone to future trials employing stem-cell-derived neurons.