N Engl J Med 2020 05;382(20):1926-1932
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.).
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.).