Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease.
Autologous transplantation of patient-specific induced pluripotent stem cell (iPSC)-derived neurons is a potential clinical approach for treatment of neurological disease. Preclinical demonstration of long-term efficacy, feasibility, and safety of iPSC-derived dopamine neurons in non-human primate models will be an important step in clinical development of cell therapy. Here, we analyzed cynomolgus monkey (CM) iPSC-derived midbrain dopamine neurons for up to 2 years following autologous transplantation in a Parkinson's disease (PD) model. In one animal, with the most successful protocol, we found that unilateral engraftment of CM-iPSCs could provide a gradual onset of functional motor improvement contralateral to the side of dopamine neuron transplantation, and increased motor activity, without a need for immunosuppression. Postmortem analyses demonstrated robust survival of midbrain-like dopaminergic neurons and extensive outgrowth into the transplanted putamen. Our proof of concept findings support further development of autologous iPSC-derived cell transplantation for treatment of PD.
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
Penelope J
PJ
Hallett
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
Michela
M
Deleidi
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
Arnar
A
Astradsson
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
Gaynor A
GA
Smith
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
Oliver
O
Cooper
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
Teresia M
TM
Osborn
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
Maria
M
Sundberg
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA; New England Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA.
Michele A
MA
Moore
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
Eduardo
E
Perez-Torres
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA; MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Anna-Liisa
AL
Brownell
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
James M
JM
Schumacher
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA; New England Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA.
Roger D
RD
Spealman
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: isacson@hms.harvard.edu.
Ole
O
Isacson
D000818:Animals; D064592:Autografts; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D008252:Macaca fascicularis; D008636:Mesencephalon / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation