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Cell Stem Cell. 2015 Mar 5;16(3):269-74. doi: 10.1016/j.stem.2015.01.018. Epub 2015 Feb 26.

Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease.

Author information

1
Neuroregeneration Research Institute, McLean Hospital and Harvard Medical School, Belmont, MA 02478, USA.
2
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.
3
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.
4
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.

Abstract

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.

PMID:
25732245
PMCID:
PMC4462124
DOI:
10.1016/j.stem.2015.01.018
[Indexed for MEDLINE]
Free PMC Article

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