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PMID: 11782534 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 4 ·2002-02-19 ·Pages 2344-9

Bjorklund LM, Sánchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O

Abstract

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.

MeSH Terms
Adrenergic Agents/pharmacology Amphetamine/pharmacology Animals Cell Culture Techniques/methods Cell Transplantation Dopamine/metabolism Dopamine Agents/pharmacology Embryo, Mammalian/cytology Immunohistochemistry Ligands Neurons/cytology,metabolism,transplantation Oxidopamine/pharmacology Parkinson Disease/therapy Rats Stem Cells/metabolism Time Factors Tomography, Emission-Computed
Chemicals
Adrenergic Agents Dopamine Agents Ligands Oxidopamine Amphetamine Dopamine
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Bjorklund Lars M
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
Chung Sangmi
Andersson Therese
Chen Iris Yin Ching
McNaught Kevin St P
Brownell Anna-Liisa
Jenkins Bruce G
Wahlestedt Claes
Kim Kwang-Soo
Isacson Ole
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.022438099
Published
2002-02-19
Epub
2002-00-08
Pages
2344-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC122367
Subset
IM
Grants
NINDS NIH HHS · P50 NS039793 · United States
NINDS NIH HHS · P50 NS39793 · United States
Corrections
CommentIn
PMID: 11854478
External Links
PubMed source DOI: 10.1073/pnas.022438099 PMC Full Text View journal details
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