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

PJ Hallett, M Deleidi, A Astradsson, GA Smith… - Cell stem cell, 2015 - cell.com
PJ Hallett, M Deleidi, A Astradsson, GA Smith, O Cooper, TM Osborn, M Sundberg
Cell stem cell, 2015cell.com
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 …
Summary
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.
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