Successful Function of Autologous iPSC-Derived Dopamine Neurons following Transplantation in a Non-Human Primate Model of Parkinson’s Disease
| Autor: | Eduardo Perez-Torres, James M. Schumacher, Teresia Osborn, Maria Sundberg, Michele A. Moore, Anna-Liisa Brownell, Arnar Astradsson, Ole Isacson, Oliver Cooper, Michela Deleidi, Penelope J. Hallett, Roger D. Spealman, Gaynor A. Smith |
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| Rok vydání: | 2015 |
| Předmět: |
Parkinson's disease
medicine.medical_treatment Induced Pluripotent Stem Cells Biology Dopamine Mesencephalon medicine Genetics Autologous transplantation Animals Humans Autografts Putamen Dopaminergic Neurons Dopaminergic Immunosuppression Parkinson Disease Cell Biology medicine.disease Transplantation Disease Models Animal Macaca fascicularis medicine.anatomical_structure nervous system Molecular Medicine Neuron Neuroscience medicine.drug Stem Cell Transplantation |
| Zdroj: | Cell Stem Cell. 16(3):269-274 |
| ISSN: | 1934-5909 |
| DOI: | 10.1016/j.stem.2015.01.018 |
| Popis: | SummaryAutologous 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. |
| Databáze: | OpenAIRE |
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