From the Departments of Neurosurgery (J.S.S., B.S.C.), Neurology (T.M.H.), and Radiology (K.K., Q.L.), the Gordon Center for Medical Imaging (K.K., Q.L.), and the Division of Neuroradiology (O.R.), Massachusetts General Hospital, the Department of Pediatrics, Computational Health Informatics Program, Boston Children's Hospital (I.-H.L., S.-W.K.), and the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber/Harvard Cancer Center (J.R.), Boston, and the Department of Psychiatry (B.M.C.) and the Molecular Neurobiology Laboratory (B.S., T.-Y.P., N.L., S.K., J.J., Y.C., H.S., J.K., T.K., P.L., K.-S.K.), McLean Hospital, Belmont - all in Massachusetts; the Departments of Neurology (C.H.) and Neurosurgery (M.K.) and the Brain and Mind Research Institute (G.A.P.), Weill Cornell Medical College, New York; the Department of Neurology, Kaiser Permanente, Irvine, CA (C.N.); and the Department of Molecular and Life Sciences, Hanyang University, Seoul, South Korea (H.S.).
N Engl J Med. 2020 May 14;382(20):1926-1932. doi: 10.1056/NEJMoa1915872.
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.).
我们报告了一例将源自患者自身诱导多能干细胞（iPSC）的中脑多巴胺能祖细胞在一名特发性帕金森病患者体内进行移植的案例。这些患者特异性祖细胞是在符合良好生产规范的条件下生成的，并具有黑质致密部神经元的表型特征；在人源化小鼠模型（涉及外周血单核细胞）中的测试表明，这些细胞对免疫原性为零。这些细胞被移植到一名帕金森病患者的壳核（先左侧，间隔 6 个月后右侧），无需免疫抑制。使用氟-18-L-二羟苯丙氨酸进行正电子发射断层扫描表明移植物存活。手术后帕金森病症状的临床评估在移植后 18 至 24 个月时稳定或改善。（由美国国立卫生研究院和其他机构资助）。
