Laboratory of Neuroscience, Felsenstein Medical Research Center, Rabin Medical Center, Tel Aviv University, Israel.
Expert Rev Neurother. 2011 Sep;11(9):1325-39. doi: 10.1586/ern.11.74.
Cell replacement therapy (CRT) offers great promise as the future of regenerative medicine in Parkinson´s disease (PD). Three decades of experiments have accumulated a wealth of knowledge regarding the replacement of dying neurons by new and healthy dopaminergic neurons transplanted into the brains of animal models and affected patients. The first clinical trials provided the proof of principle for CRT in PD. In these experiments, intrastriatal transplantation of human embryonic mesencephalic tissue reinnervated the striatum, restored dopamine levels and showed motor improvements. Sequential controlled studies highlighted several problems that should be addressed prior to the wide application of CRT for PD patients. Moreover, owing to ethical and practical problems, embryonic stem cells require replacement by better-suited stem cells. Several obstacles remain to be surpassed, including identifying the best source of stem cells for A9 dopaminergic neuron generation, eliminating the risk of tumor formation and the development of graft-induced dyskinesias, and standardizing dopaminergic cell production in order to enable clinical application. In this article, we present an update on CRT for PD, reviewing the research milestones, various stem cells used and tailored differentiation methods, and analyze the information gained from the clinical trials.
细胞替代疗法 (CRT) 有望成为帕金森病 (PD) 再生医学的未来。三十年来的实验积累了大量关于通过将新的和健康的多巴胺能神经元移植到动物模型和受影响的患者的大脑中来替代死亡神经元的知识。第一批临床试验为 PD 中的 CRT 提供了原理证明。在这些实验中，纹状体内移植人胚胎中脑组织使纹状体重新支配，恢复多巴胺水平并显示运动改善。连续对照研究突出了在广泛应用 CRT 治疗 PD 患者之前应解决的几个问题。此外，由于伦理和实际问题，胚胎干细胞需要更好的干细胞来替代。仍有几个障碍需要克服，包括确定生成 A9 多巴胺能神经元的最佳干细胞来源，消除肿瘤形成和移植物诱导运动障碍的风险，以及标准化多巴胺能细胞的产生，以便能够进行临床应用。在本文中，我们介绍了 PD 中 CRT 的最新进展，回顾了研究里程碑、使用的各种干细胞和定制的分化方法，并分析了临床试验获得的信息。
