Jang Se Eun, Qiu Lifeng, Chan Ling Ling, Tan Eng-King, Zeng Li
Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore.
Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore.
Front Neurosci. 2020 Oct 16;14:558532. doi: 10.3389/fnins.2020.558532. eCollection 2020.
Curative therapies or treatments reversing the progression of Parkinson's disease (PD) have attracted considerable interest in the last few decades. PD is characterized by the gradual loss of dopaminergic (DA) neurons and decreased striatal dopamine levels. Current challenges include optimizing neuroprotective strategies, developing personalized drug therapy, and minimizing side effects from the long-term prescription of pharmacological drugs used to relieve short-term motor symptoms. Transplantation of DA cells into PD patients' brains to replace degenerated DA has the potential to change the treatment paradigm. Herein, we provide updates on current progress in stem cell-derived DA neuron transplantation as a therapeutic alternative for PD. We briefly highlight cell sources for transplantation and focus on cell assessment methods such as identification of genetic markers, single-cell sequencing, and imaging modalities used to access cell survival and function. More importantly, we summarize clinical reports of patients who have undergone cell-derived transplantation in PD to better perceive lessons that can be drawn from past and present clinical outcomes. Modifying factors include (1) source of the stem cells, (2) quality of the stem cells, (3) age of the patient, (4) stage of disease progression at the time of cell therapy, (5) surgical technique/practices, and (6) the use of immunosuppression. We await the outcomes of joint efforts in clinical trials around the world such as NYSTEM and CiRA to further guide us in the selection of the most suitable parameters for cell-based neurotransplantation in PD.
在过去几十年中，能够逆转帕金森病（PD）进展的治愈性疗法或治疗手段引起了广泛关注。PD的特征是多巴胺能（DA）神经元逐渐丧失以及纹状体多巴胺水平降低。当前的挑战包括优化神经保护策略、开发个性化药物治疗以及尽量减少用于缓解短期运动症状的药物长期处方所带来的副作用。将DA细胞移植到PD患者大脑中以替代退化的DA具有改变治疗模式的潜力。在此，我们提供关于干细胞衍生的DA神经元移植作为PD治疗替代方案的当前进展的最新情况。我们简要强调移植的细胞来源，并专注于细胞评估方法，如遗传标记物的鉴定、单细胞测序以及用于评估细胞存活和功能的成像方式。更重要的是，我们总结了接受PD细胞衍生移植的患者的临床报告，以便更好地了解从过去和当前临床结果中可以吸取的经验教训。影响因素包括：（1）干细胞来源；（2）干细胞质量；（3）患者年龄；（4）细胞治疗时疾病进展阶段；（5）手术技术/操作；（6）免疫抑制的使用。我们期待全球范围内如NYSTEM和CiRA等临床试验的共同努力成果，以进一步指导我们为PD基于细胞的神经移植选择最合适的参数。
