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, Ole Isacson

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2127-2139
Number of pages13
JournalBrain
Volume131
Issue number8
DOIs
Publication statusPublished - 2008 Aug

Keywords

  • Midbrain
  • Parkinson's disease
  • Parthenogenesis
  • Stem cells
  • Transplantation

ASJC Scopus subject areas

  • Clinical Neurology

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    Sanchez-Pernaute, R., Lee, H., Patterson, M., Reske-Nielsen, C., Yoshizaki, T., Sonntag, K. C., Studer, L., & Isacson, O. (2008). Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease. Brain, 131(8), 2127-2139. https://doi.org/10.1093/brain/awn144