Stem cell-based therapy for Parkinson's disease.
Motor dysfunctions in Parkinson's disease are considered to be primarily due to the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Pharmacological therapies based on the principle of dopamine replacement are extremely valuable, but suffer from two main drawbacks: troubling side effects (e.g. dyskinesia) and loss of efficacy with disease progression. Transplantation of embryonic dopaminergic neurons has emerged as a therapeutic alternative. Enthusiasm following the success of the initial open-label trials has been dampened by the negative outcome of double-blind placebo controlled trials. Additionally, the emergence of graft-related dyskinesia indicates that the experimental grafting procedure requires further refinement before it can be developed into a therapy. Shortage of embryonic donor tissue limits large-scale clinical transplantation trials. We review three of the most attractive tissue sources of dopaminergic neurons for cell replacement therapy: human embryonic ventral mesencephalic tissue, embryonic and adult multipotent region-specific stem cells and embryonic stem cells. Recent developments in embryonic stem cell research and on their implications for a future transplantation therapy in Parkinson's disease are described. Finally, we discuss how human embryonic stem cells can be differentiated into dopaminergic neurons, and issues such as the numbers of dopaminergic neurons required for success and the risk for teratoma formation after implantation.
Correia
Ana Sofia
AS
Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden. Sofia.Correia@med.lu.se
Anisimov
Sergey V
SV
Li
Jia-Yi
JY
Brundin
Patrik
P
D000818:Animals; D002454:Cell Differentiation; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010300:Parkinson Disease / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000941:ethics / Q000379:methods*; D013724:Teratoma / Q000209:etiology / Q000517:prevention & control
D004298:Dopamine