Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease Journal Article
| Authors: | Sanchez-Pernaute, R.; Lee, H.; Patterson, M.; Reske-Nielsen, C.; Yoshizaki, T.; Sonntag, K. C.; Studer, L.; Isacson, O. |
| Article Title: | Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease |
| 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. © The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. |
| Keywords: | signal transduction; survival; controlled study; protein expression; treatment outcome; nonhuman; phenotype; animals; cell survival; cell function; cell maturation; embryonic stem cell; cell line; animal experiment; animal model; in vivo study; cell differentiation; neurons; in vitro study; transplantation; fibroblast growth factor 2; brain derived neurotrophic factor; rat; stem cells; cyclic amp; embryonic stem cells; rats; ascorbic acid; midbrain; mesencephalon; rats, sprague-dawley; motor performance; motor activity; parkinson disease; wnt proteins; dopamine; dopaminergic nerve cell; fibroblast growth factor; fibroblast growth factors; wnt5a protein; transforming growth factor beta3; glial cell line derived neurotrophic factor; synaptic transmission; nerve fiber growth; parkinson's disease; parthenogenesis; oxidopamine; parkinsonian disorders |
| Journal Title: | Brain |
| Volume: | 131 |
| Issue: | 8 |
| ISSN: | 0006-8950 |
| Publisher: | Oxford University Press |
| Date Published: | 2008-08-01 |
| Start Page: | 2127 |
| End Page: | 2139 |
| Language: | English |
| DOI: | 10.1093/brain/awn144 |
| PUBMED: | 18669499 |
| PROVIDER: | scopus |
| PMCID: | PMC2724903 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 27" - "Export Date: 17 November 2011" - "CODEN: BRAIA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work