Embryonic Stem Cells Relieve Parkinson's Disease in Rats
Lars M. Björklund*, [dagger], [Dagger] , Rosario Sánchez-Pernaute*, [dagger] ,§, Sangmi Chung*,¶, Therese Andersson*,¶, [||] , Iris Yin Ching Chen§, Kevin St. P. McNaught*, [dagger], Anna-Liisa Brownell*,§, Bruce G. Jenkins§, Claes Wahlestedt [||] , Kwang-Soo Kim*,¶, and Ole Isacson*, [dagger], [Dagger] ,** "Embryonic Stem Cells Develop into Functional Dopaminergic Neurons after Transplantation in a Parkinson Rat Model," Proc. Natl. Acad. Sci. USA, Vol. 10, p. 1073 (January 8, 2002).
--------------------------------------------------------------------------------------------------------
* Udall Parkinson's Disease Research Center of Excellence,
[dagger] Neuroregeneration Laboratories, and
¶ Molecular Neurobiology Laboratory
McLean Hospital/Harvard Medical School
115 Mill Street, Belmont, MA 02478
Departments of
§ Radiology and
** Neurology,
Massachusetts General Hospital and Program in Neuroscience
Harvard Medical School
Boston, MA 02114; and
[||] Karolinska Institute, SE-17177 Stockholm, SWEDEN
____________________________________________________
[Dagger] To whom reprint requests may be addressed:
E-mail:
E-mail:
______________________________________________________________________
Edited by Gerald D. Fischbach, Columbia University College of Physicians and Surgeons, New York, NY, and approved November 29, 2001 (received for review August 20, 2001)
______________________________________________________________________
ABSTRACT:
Although implantation of Fetal Dopamine (DA) neurons can reduce Parkinsonism in human 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 (PET) and functional Magnetic Resonance Imaging (fMRI) 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.