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

Lars M. Björklund, Rosario Sánchez-Pernaute, Sangmi Chung, Therese Andersson, Iris Yin Ching Chen, Kevin St P McNaught, Anna Liisa Brownell, Bruce G. Jenkins, Claes R Wahlestedt, Kwang Soo Kim, Ole Isacson

Research output: Contribution to journalArticle

972 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2344-2349
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number4
DOIs
StatePublished - Feb 19 2002
Externally publishedYes

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Dopaminergic Neurons
Embryonic Stem Cells
Transplantation
Dopamine
Parkinsonian Disorders
Positron-Emission Tomography
Parkinson Disease
Animal Models
Hemodynamics
Magnetic Resonance Imaging
Tissue Donors
Brain

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. / Björklund, Lars M.; Sánchez-Pernaute, Rosario; Chung, Sangmi; Andersson, Therese; Chen, Iris Yin Ching; McNaught, Kevin St P; Brownell, Anna Liisa; Jenkins, Bruce G.; Wahlestedt, Claes R; Kim, Kwang Soo; Isacson, Ole.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 4, 19.02.2002, p. 2344-2349.

Research output: Contribution to journalArticle

Björklund, LM, Sánchez-Pernaute, R, Chung, S, Andersson, T, Chen, IYC, McNaught, KSP, Brownell, AL, Jenkins, BG, Wahlestedt, CR, Kim, KS & Isacson, O 2002, '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, pp. 2344-2349. https://doi.org/10.1073/pnas.022438099
Björklund, Lars M. ; Sánchez-Pernaute, Rosario ; Chung, Sangmi ; Andersson, Therese ; Chen, Iris Yin Ching ; McNaught, Kevin St P ; Brownell, Anna Liisa ; Jenkins, Bruce G. ; Wahlestedt, Claes R ; Kim, Kwang Soo ; Isacson, Ole. / Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 4. pp. 2344-2349.
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