Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of Parkinson disease.
The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects. Microdialysis in grafted animals showed that dopamine (DA) release was induced by depolarization and pharmacological stimulants. Positron emission tomography measured the expression of presynaptic dopamine transporters in the graft and also showed that the number of postsynaptic DA D(2) receptors was normalized in the host striatum. These data suggest that ES cell-derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons.
Rodríguez-Gómez
Jose A
JA
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, Porter Neuroscience Research Center, National Institute of Health, Bethesda, Maryland 20892, USA.
Lu
Jian-Qiang
JQ
Velasco
Iván
I
Rivera
Seth
S
Zoghbi
Sami S
SS
Liow
Jeih-San
JS
Musachio
John L
JL
Chin
Frederick T
FT
Toyama
Hiroshi
H
Seidel
Jurgen
J
Green
Michael V
MV
Thanos
Panayotis K
PK
Ichise
Masanori
M
Pike
Victor W
VW
Innis
Robert B
RB
McKay
Ron D G
RD
D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000473:pathology / Q000502:physiology*; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D017551:Microdialysis; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D020734:Parkinsonian Disorders / Q000473:pathology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013239:Stereotyped Behavior
D006892:Hydroxydopamines; C027802:5-hydroxydopamine; D004298:Dopamine