Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model

被引:874
作者
Björklund, LM
Sánchez-Pernaute, R
Chung, SM
Andersson, T
Chen, IYC
McNaught, KS
Brownell, AL
Jenkins, BG
Wahlestedt, C
Kim, KS
Isacson, O
机构
[1] Harvard Univ, McLean Hosp, Sch Med, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA
[2] Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, Belmont, MA 02478 USA
[3] Harvard Univ, McLean Hosp, Sch Med, Mol Neurobiol Lab, Belmont, MA 02478 USA
[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA
[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA
[6] Harvard Univ, Program Neurosci, Sch Med, Boston, MA 02114 USA
[7] Karolinska Inst, SE-17177 Stockholm, Sweden
关键词
D O I
10.1073/pnas.022438099
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2344 / 2349
页数:6
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