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Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model.
- Source :
-
Nature [Nature] 2017 Aug 30; Vol. 548 (7669), pp. 592-596. - Publication Year :
- 2017
-
Abstract
- Induced pluripotent stem cells (iPS cells) are a promising source for a cell-based therapy to treat Parkinson's disease (PD), in which midbrain dopaminergic neurons progressively degenerate. However, long-term analysis of human iPS cell-derived dopaminergic neurons in primate PD models has never been performed to our knowledge. Here we show that human iPS cell-derived dopaminergic progenitor cells survived and functioned as midbrain dopaminergic neurons in a primate model of PD (Macaca fascicularis) treated with the neurotoxin MPTP. Score-based and video-recording analyses revealed an increase in spontaneous movement of the monkeys after transplantation. Histological studies showed that the mature dopaminergic neurons extended dense neurites into the host striatum; this effect was consistent regardless of whether the cells were derived from patients with PD or from healthy individuals. Cells sorted by the floor plate marker CORIN did not form any tumours in the brains for at least two years. Finally, magnetic resonance imaging and positron emission tomography were used to monitor the survival, expansion and function of the grafted cells as well as the immune response in the host brain. Thus, this preclinical study using a primate model indicates that human iPS cell-derived dopaminergic progenitors are clinically applicable for the treatment of patients with PD.
- Subjects :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Adult
Aged
Aged, 80 and over
Animals
Cell Proliferation
Cell Survival
Dopaminergic Neurons immunology
Humans
Macaca fascicularis
Magnetic Resonance Imaging
Male
Mesencephalon cytology
Movement
Neostriatum cytology
Neurites
Parkinson Disease etiology
Parkinson Disease physiopathology
Positron-Emission Tomography
Serine Endopeptidases analysis
Serine Endopeptidases metabolism
Disease Models, Animal
Dopaminergic Neurons cytology
Dopaminergic Neurons transplantation
Induced Pluripotent Stem Cells cytology
Parkinson Disease pathology
Parkinson Disease therapy
Regenerative Medicine methods
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 548
- Issue :
- 7669
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 28858313
- Full Text :
- https://doi.org/10.1038/nature23664