Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Neuroscience. 2021 May 21;463:370-382. doi: 10.1016/j.neuroscience.2021.03.022. Epub 2021 Mar 26.
Parkinson's disease (PD) is characterized by tremor, rigidity, and bradykinesia. PD is caused mainly by depletion of the nigrostriatal pathway. Conventional medications such as levodopa are highly effective in the early stage of PD; however, these medications fail to prevent the underlying neurodegeneration. Cell replacement therapy (CRT) is a strategy to achieve long-term motor improvements by preventing or slowing disease progression. Replacement therapy can also increase the number of surviving dopaminergic neurons, an outcome confirmed by positron emission tomography and immunostaining. Several promising cell sources offer authentic and functional dopaminergic replacement neurons. These cell sources include fetal ventral mesencephalic tissue, embryonic stem cells (ESCs), neural stem cells (NSCs), mesenchymal stem cells (MSCs) from various tissues, induced pluripotent stem cells (iPSCs), and induced neural cells. To fully develop the potential of CRT, we need to recognize the advantages and limitations of these cell sources. For example, although fetal ventral midbrain is efficacious in some patients, its ethical issues and the existence of graft-induced dyskinesias (GID) have prevented its use in large-scale clinical applications. ESCs have reliable isolation protocols and the potential to differentiate into dopaminergic progenitors. iPSCs and induced neural cells are suitable for autologous grafting. Here we review milestone improvements and emerging sources for cell-based PD therapy to serve as a framework for clinicians and a key reference to develop replacement therapy for other neurological disorders.
帕金森病（PD）的特征是震颤、僵硬和运动迟缓。PD 主要是由黑质纹状体通路的耗竭引起的。左旋多巴等传统药物在 PD 的早期非常有效；然而，这些药物无法预防潜在的神经退行性变。细胞替代疗法（CRT）是一种通过预防或减缓疾病进展来实现长期运动改善的策略。替代疗法还可以增加存活的多巴胺能神经元的数量，这一结果通过正电子发射断层扫描和免疫染色得到了证实。几种有前途的细胞来源提供了真实和功能上的多巴胺能替代神经元。这些细胞来源包括胎儿中脑腹侧组织、胚胎干细胞（ESCs）、神经干细胞（NSCs）、来自各种组织的间充质干细胞（MSCs）、诱导多能干细胞（iPSCs）和诱导神经细胞。为了充分发挥 CRT 的潜力，我们需要认识到这些细胞来源的优势和局限性。例如，尽管胎脑中脑腹侧在一些患者中有效，但它的伦理问题和移植物诱导的运动障碍（GID）的存在阻止了其在大规模临床应用中的使用。ESCs 具有可靠的分离方案和分化为多巴胺能祖细胞的潜力。iPSCs 和诱导的神经细胞适合自体移植。在这里，我们回顾了基于细胞的 PD 治疗的里程碑式进展和新兴来源，为临床医生提供了一个框架，并为开发其他神经退行性疾病的替代疗法提供了一个关键参考。
