Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model.
Although implantation of fetal dopamine (DA) neurons can reduce parkinsonism in patients, current methods are rudimentary, and a reliable donor cell source is lacking. We show that transplanting low doses of undifferentiated mouse embryonic stem (ES) cells into the rat striatum results in a proliferation of ES cells into fully differentiated DA neurons. ES cell-derived DA neurons caused gradual and sustained behavioral restoration of DA-mediated motor asymmetry. Behavioral recovery paralleled in vivo positron emission tomography and functional magnetic resonance imaging data demonstrating DA-mediated hemodynamic changes in the striatum and associated brain circuitry. These results demonstrate that transplanted ES cells can develop spontaneously into DA neurons. Such DA neurons can restore cerebral function and behavior in an animal model of Parkinson's disease.
Bjorklund
Lars M
LM
Udall Parkinson's Disease Research Center of Excellence, Neuroregeneration Laboratories, and Molecular Neurobiology Laboratory, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
Sánchez-Pernaute
Rosario
R
Chung
Sangmi
S
Andersson
Therese
T
Chen
Iris Yin Ching
IY
McNaught
Kevin St P
KS
Brownell
Anna-Liisa
AL
Jenkins
Bruce G
BG
Wahlestedt
Claes
C
Kim
Kwang-Soo
KS
Isacson
Ole
O
D018663:Adrenergic Agents / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D017690:Cell Transplantation; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology*; D007150:Immunohistochemistry; D008024:Ligands; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000628:therapy*; D051381:Rats; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D014055:Tomography, Emission-Computed
D018663:Adrenergic Agents; D015259:Dopamine Agents; D008024:Ligands; D016627:Oxidopamine; D000661:Amphetamine; D004298:Dopamine