Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson's Disease
Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson's Disease
复制标题
DOI：
10.1056/nejmoa1915872
复制
发表时间：
2020-05-14
影响因子：
158.5
通讯作者：
Kim, Kwang-Soo
中科院分区：
文献类型：
--
作者：
Schweitzer, Jeffrey S.;Song, Bin;Kim, Kwang-Soo
我们报道了在特发性帕金森病患者中植入患者来源的中脑多巴胺能前体细胞，体外分化自体诱导多能干细胞(IPSCs)。患者特有的祖细胞是在良好的制造实践条件下生产的，其特征是具有黑质致密部神经元的表型特性；在人源化的小鼠模型(涉及外周血单核细胞)中进行的测试表明，这些细胞缺乏免疫原性。这些细胞被植入帕金森氏病患者的壳核(左半球和右半球，相隔6个月)，而不需要免疫抑制。使用氟-18-L-二羟基苯丙氨酸的正电子发射断层扫描显示移植物存活。术后帕金森病症状的临床测量在植入后18至24个月稳定或改善。(由美国国立卫生研究院和其他机构资助。)从患者诱导的多能干细胞中提取的多巴胺能祖细胞被双侧植入壳核。临床和PET研究表明，在24个月的时间里，细胞存活和临床稳定，没有运动障碍。
We report the implantation of patient-derived midbrain dopaminergic progenitor cells, differentiated in vitro from autologous induced pluripotent stem cells (iPSCs), in a patient with idiopathic Parkinson's disease. The patient-specific progenitor cells were produced under Good Manufacturing Practice conditions and characterized as having the phenotypic properties of substantia nigra pars compacta neurons; testing in a humanized mouse model (involving peripheral-blood mononuclear cells) indicated an absence of immunogenicity to these cells. The cells were implanted into the putamen (left hemisphere followed by right hemisphere, 6 months apart) of a patient with Parkinson's disease, without the need for immunosuppression. Positron-emission tomography with the use of fluorine-18-L-dihydroxyphenylalanine suggested graft survival. Clinical measures of symptoms of Parkinson's disease after surgery stabilized or improved at 18 to 24 months after implantation. (Funded by the National Institutes of Health and others.)Dopaminergic progenitor cells that were derived from a patient's induced pluripotent stem cells were implanted bilaterally in the putamen. Clinical and PET studies suggested survival of the cells and clinical stability over a period of 24 months, without dyskinesias.