The Institute for Translational Medicine, Affiliated Hospital, Shandong University, Jinan, Shandong, China.
The Institute for Tissue Engineering and Regenerative Medicine, Liaocheng University/Liaocheng People's Hospital, Liaocheng, Shandong, China.
Adv Exp Med Biol. 2020;1266:21-38. doi: 10.1007/978-981-15-4370-8_3.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases caused by specific degeneration and loss of dopamine neurons in substantia nigra of the midbrain. PD is clinically characterized by motor dysfunctions and non-motor symptoms. Even though the dopamine replacement can improve the motor symptoms of PD, it cannot stop the neural degeneration and disease progression. Electrical deep brain stimulation (DBS) to the specific brain areas can improve the symptoms, but it eventually loses the effectiveness. Stem cell transplantation provides an exciting potential for the treatment of PD. Current available cell sources include neural stem cells (NSCs) from fetal brain tissues, human embryonic stem cells (hESCs) isolated from blastocyst, and induced pluripotent stem cells (iPSCs) reprogrammed from the somatic cells such as the fibroblasts and blood cells. Here, we summarize the research advance in experimental and clinical studies to transplant these cells into animal models and clinical patients, and specifically highlight the studies to use hESCs /iPSCs-derived dopaminergic precursor cells and dopamine neurons for the treatment of PD, at last propose future challenges for developing clinical-grade dopaminergic cells for treating the PD.
帕金森病(PD)是一种最常见的神经退行性疾病,由中脑黑质区特定的多巴胺神经元变性和丧失引起。PD 的临床特征为运动功能障碍和非运动症状。尽管多巴胺替代疗法可以改善 PD 的运动症状,但它不能阻止神经变性和疾病进展。对特定脑区进行电深部脑刺激(DBS)可以改善症状,但最终会失去疗效。干细胞移植为 PD 的治疗提供了令人兴奋的潜力。目前可用的细胞来源包括来自胎儿脑组织的神经干细胞(NSCs)、从囊胚中分离出的人胚胎干细胞(hESCs)以及从成纤维细胞和血细胞等体细胞重编程的诱导多能干细胞(iPSCs)。在这里,我们总结了将这些细胞移植到动物模型和临床患者中的实验和临床研究进展,并特别强调了使用 hESCs/iPSCs 衍生的多巴胺能前体细胞和多巴胺神经元治疗 PD 的研究,最后提出了为治疗 PD 开发临床级多巴胺能细胞的未来挑战。