Dong Wenjing, Liu Shuyi, Li Shangang, Wang Zhengbo
State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan Province, China.
Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan Province, China.
Neural Regen Res. 2024 Nov 1;19(11):2444-2455. doi: 10.4103/1673-5374.390965. Epub 2023 Dec 15.
Parkinson's disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson's disease. The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson's disease, which could substantially alleviate the symptoms of Parkinson's disease in clinical practice. However, ethical issues and tumor formation were limitations of its clinical application. Induced pluripotent stem cells can be acquired without sacrificing human embryos, which eliminates the huge ethical barriers of human stem cell therapy. Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons, without the need for intermediate proliferation states, thus avoiding issues of immune rejection and tumor formation. Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson's disease. However, there are also ethical concerns and the risk of tumor formation that need to be addressed. This review highlights the current application status of cell reprogramming in the treatment of Parkinson's disease, focusing on the use of induced pluripotent stem cells in cell replacement therapy, including preclinical animal models and progress in clinical research. The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson's disease, as well as the controversy surrounding in vivo reprogramming. These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson's disease.
帕金森病的典型特征是黑质致密部多巴胺能神经元的进行性丧失。许多研究基于补充丧失的多巴胺能神经元来治疗帕金森病。细胞替代疗法的最初策略是使用人胎儿腹侧中脑和人胚胎干细胞来治疗帕金森病,这在临床实践中可显著缓解帕金森病的症状。然而,伦理问题和肿瘤形成是其临床应用的局限性。诱导多能干细胞可以在不牺牲人类胚胎的情况下获得,这消除了人类干细胞治疗的巨大伦理障碍。另一种被广泛考虑的神经元再生策略是将成纤维细胞和星形胶质细胞直接重编程为神经元,无需中间增殖状态,从而避免免疫排斥和肿瘤形成问题。诱导多能干细胞和谱系细胞的直接重编程在帕金森病治疗中均已显示出有前景的结果。然而,也存在伦理问题以及需要解决的肿瘤形成风险。本综述重点介绍了细胞重编程在帕金森病治疗中的当前应用状况,着重于诱导多能干细胞在细胞替代疗法中的应用,包括临床前动物模型和临床研究进展。综述还讨论了谱系细胞直接重编程在帕金森病治疗中的进展,以及围绕体内重编程的争议。这些发现表明,细胞重编程作为治疗帕金森病的潜在策略可能具有巨大潜力。