Parkinson's disease (PD) is the second most common progressive neurodegenerative disease, affecting 1-2% of people over 65. The classic motor symptoms of PD result from selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in a loss of their long axonal projections to the striatum. Current treatment strategies such as dopamine replacement and deep brain stimulation (DBS) can only minimize the symptoms of nigrostriatal degeneration, not directly replace the lost pathway. Regenerative medicine-based solutions are being aggressively pursued with the goal of restoring dopamine levels in the striatum, with several emerging techniques attempting to reconstruct the entire nigrostriatal pathway-a key goal to recreate feedback pathways to ensure proper dopamine regulation. Although many pharmacological, genetic, and optogenetic treatments are being developed, this article focuses on the evolution of transplant therapies for the treatment of PD, including fetal grafts, cell-based implants, and more recent tissue-engineered constructs. Attention is given to cell/tissue sources, efficacy to date, and future challenges that must be overcome to enable robust translation into clinical use. Emerging regenerative medicine therapies are being developed using neurons derived from autologous stem cells, enabling the construction of patient-specific constructs tailored to their particular extent of degeneration. In the upcoming era of restorative neurosurgery, such constructs may directly replace SNpc neurons, restore axon-based dopaminergic inputs to the striatum, and ameliorate motor deficits. These solutions may provide a transformative and scalable solution to permanently replace lost neuroanatomy and improve the lives of millions of people afflicted by PD.

中文翻译：

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帕金森氏病的新兴再生医学和组织工程策略。

帕金森氏病（PD）是第二种最常见的进行性神经退行性疾病，影响1-2％的65岁以上人群。PD的典型运动症状是由黑质致密部（SNpc）中的多巴胺能神经元选择性变性导致的，它们的长轴突投影丢失到纹状体。当前的治疗策略，例如多巴胺替代和深部脑刺激（DBS），只能使黑质纹状体变性的症状最小化，而不能直接替代丢失的途径。为了恢复纹状体中的多巴胺水平，正在积极寻求基于再生药物的解决方案，同时尝试了几种新兴技术来尝试重建整个黑纹状体途径，这是重建反馈途径以确保适当的多巴胺调节的关键目标。尽管许多药理学 遗传和光遗传学治疗方法正在开发中，本文重点介绍用于治疗PD的移植疗法的发展，包括胎儿移植物，基于细胞的植入物以及最近的组织工程构建物。要注意细胞/组织的来源，迄今为止的功效以及为将其可靠地转化为临床用途而必须克服的未来挑战。正在使用源自自体干细胞的神经元开发新兴的再生医学疗法，从而能够构建针对患者特定变性程度的患者特异性构建体。在即将到来的修复性神经外科时代，此类构建体可直接替代SNpc神经元，将纹状体的轴突基多巴胺能输入恢复，并改善运动功能障碍。