Yi Ling-Xiao, Woon Hui Ren, Saw Genevieve, Zeng Li, Tan Eng King, Zhou Zhi Dong
National Neuroscience Institute, Singapore.
Nanyang Technology University, Singapore.
Neural Regen Res. 2025 Nov 1;20(11):3193-3206. doi: 10.4103/NRR.NRR-D-24-00771. Epub 2024 Dec 7.
The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease, the second most common human neurodegenerative disease. Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear, the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy. The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons, which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies. The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells. The benefits of induced pluripotent stem cell-based research are highlighted. Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared. The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated. Finally, limitations, challenges, and future directions of induced pluripotent stem cell-based approaches are analyzed and proposed, which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.
在受影响患者大脑中多巴胺能神经元的渐进性丧失是帕金森病的病理特征之一，帕金森病是人类第二常见的神经退行性疾病。尽管帕金森病中多巴胺能神经元变性的详细发病机制仍不清楚，但干细胞方法的进展已显示出在帕金森病研究和治疗方面的前景。诱导多能干细胞已被广泛用于生成多巴胺能神经元，这为增进我们对帕金森病发病机制的理解提供了有价值的见解，并有助于抗帕金森病治疗。本综述讨论了从诱导多能干细胞生成和分化多巴胺能神经元的诱导多能干细胞技术的实际方法和潜在应用。强调了基于诱导多能干细胞研究的益处。比较了从诱导多能干细胞分化出多巴胺能神经元的各种方案。评估了与传统二维细胞培养相比新兴的基于三维的脑类器官模型。最后，分析并提出了基于诱导多能干细胞方法的局限性、挑战和未来方向，这对诱导多能干细胞相关技术在帕金森病中的未来应用具有重要意义。
