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

Hallett, Penelope J., Deleidi, Michela, Astradsson, Arnar, Smith, Gaynor A., Cooper, Oliver, Osborn, Teresia M., Sundberg, Maria, Moore, Michele A., Perez-Torres, Eduardo, Brownell, Anna-Liisa, Schumacher, James M., Spealman, Roger D. and Isacson, Ole 2015. Successful function of Autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease. Cell Stem Cell 16 (3) , pp. 269-274. 10.1016/j.stem.2015.01.018

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 1934-5909
Date of Acceptance: 30 January 2015
Last Modified: 05 Nov 2020 14:48
URI: http://orca.cardiff.ac.uk/id/eprint/106221

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