Influence of cell preparation and target location on the behavioral recovery after striatal transplantation of fetal dopaminergic neurons in a primate model of Parkinson’s disease

The clinical trials with intrastriatal transplantation of human fetal mesencephalic tissue, rich in dopaminergic neurons, in Parkinson's disease (PD) patients show that cell replacement can work and in some cases induce major, long-lasting improvement. However, owing to poor tissue availability, this approach can only be applied in very few patients, and standardization is difficult, leading to wide variation in functional outcome. Stem cells and reprogrammed cells could potentially be used to produce dopaminergic neurons for transplantation. Importantly, dopaminergic neurons of the correct substantia nigra phenotype can now be generated from human embryonic stem cells in large numbers and standardized preparations, and will soon be ready for application in patients. Also, human induced pluripotent stem cell-derived dopaminergic neurons are being considered for clinical translation. Available data justify moving forward in a responsible way with these dopaminergic neurons, which should be tested, using optimal patient selection, cell preparation and transplantation procedures, in controlled clinical studies.

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Behavioral Recovery in a Primate Model of Parkinson's Disease by Triple Transduction of Striatal Cells with Adeno-Associated Viral Vectors Expressing Dopamine-Synthesizing Enzymes

Human Gene Therapy ◽

10.1089/10430340252792486 ◽

2002 ◽

Vol 13 (3) ◽

pp. 345-354 ◽

Cited By ~ 133

Author(s):

Shin-Ichi Muramatsu ◽

Ken-Ichi Fujimoto ◽

Kunihiko Ikeguchi ◽

Nami Shizuma ◽

Katsuyoshi Kawasaki ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Viral Vectors ◽

Behavioral Recovery ◽

Primate Model

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Faculty Opinions recommendation of Conditional expression of Parkinson's disease-related mutant α-synuclein in the midbrain dopaminergic neurons causes progressive neurodegeneration and degradation of transcription factor nuclear receptor related 1.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717953615.793459220 ◽

2012 ◽

Author(s):

Patrik Brundin ◽

Jennifer Steiner

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Transcription Factor ◽

Nuclear Receptor ◽

Dopaminergic Neurons ◽

Midbrain Dopaminergic Neurons ◽

Conditional Expression ◽

Progressive Neurodegeneration

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Faculty Opinions recommendation of Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.729804646.793537492 ◽

2017 ◽

Author(s):

Ole Isacson ◽

Teresia Osborn

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Disease Model ◽

Ips Cell

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Comparison of Cytocidal Activities of L-DOPA and Dopamine in S. cerevisiae and C. glabrata

Current Bioactive Compounds ◽

10.2174/1573407214666180108144216 ◽

2020 ◽

Vol 16 (1) ◽

pp. 90-93

Author(s):

Carmen E. Iriarte ◽

Ian G. Macreadie

Keyword(s):

Saccharomyces Cerevisiae ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Candida Glabrata ◽

High Sensitivity ◽

Time Dependent ◽

Colony Forming Units ◽

Dependent Cell ◽

The Brain

Background: Parkinson's Disease results from a loss of dopaminergic neurons, and reduced levels of the neurotransmitter dopamine. Parkinson's Disease treatments involve increasing dopamine levels through administration of L-DOPA, which can cross the blood brain barrier and be converted to dopamine in the brain. The toxicity of dopamine has previously studied but there has been little study of L-DOPA toxicity. Methods: We have compared the toxicity of dopamine and L-DOPA in the yeasts, Saccharomyces cerevisiae and Candida glabrata by cell viability assays, measuring colony forming units. Results: L-DOPA and dopamine caused time-dependent cell killing in Candida glabrata while only dopamine caused such effects in Saccharomyces cerevisiae. The toxicity of L-DOPA is much lower than dopamine. Conclusion: Candida glabrata exhibits high sensitivity to L-DOPA and may have advantages for studying the cytotoxicity of L-DOPA.

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