Journal Article

Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease

Rosario Sanchez-Pernaute, Hyojin Lee, Michaela Patterson, Casper Reske-Nielsen, Takahito Yoshizaki, Kai C. Sonntag, Lorenz Studer and Ole Isacson

in Brain

Published on behalf of The Guarantors of Brain

Volume 131, issue 8, pages 2127-2139
Published in print August 2008 | ISSN: 0006-8950
Published online July 2008 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awn144
Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease

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The identity and functional potential of dopamine neurons derived in vitro from embryonic stem cells are critical for the development of a stem cell-based replacement therapy for Parkinson's disease. Using a parthenogenetic primate embryonic stem cell line, we have generated dopamine neurons that display persistent expression of midbrain regional and cell-specific transcription factors, which establish their proper identity and allow for their survival. We show here that transplantation of parthenogenetic dopamine neurons restores motor function in hemi-parkinsonian, 6-hydroxy-dopamine-lesioned rats. Exposure to Wnt5a and fibroblast growth factors (FGF) 20 and 2 at the final stage of in vitro differentiation enhanced the survival of dopamine neurons and, correspondingly, the extent of motor recovery of transplanted animals. Importantly for future development of clinical applications, dopamine neurons were post-mitotic at the time of transplantation and there was no tumour formation. These data provide proof for the concept that parthenogenetic stem cells are a suitable source of functional neurons for therapeutic applications.

Keywords: stem cells; transplantation; midbrain; Parkinson's disease; parthenogenesis

Journal Article.  7612 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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