TY - JOUR
T1 - Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease
AU - Sanchez-Pernaute, Rosario
AU - Lee, Hyojin
AU - Patterson, Michaela
AU - Reske-Nielsen, Casper
AU - Yoshizaki, Takahito
AU - Sonntag, Kai C.
AU - Studer, Lorenz
AU - Isacson, Ole
N1 - Funding Information:
This study was supported by the Harvard Stem Cell Institute, the Starr Fundation and the National Institutes of Health NINDS P50 NS-39793 and R01 NS-052671. We are grateful to Yalda Sadeghi and Shreeya Karki for technical help.
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - Midbrain
KW - Parkinson's disease
KW - Parthenogenesis
KW - Stem cells
KW - Transplantation
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U2 - 10.1093/brain/awn144
DO - 10.1093/brain/awn144
M3 - Article
C2 - 18669499
AN - SCOPUS:49449109011
SN - 0006-8950
VL - 131
SP - 2127
EP - 2139
JO - Brain
JF - Brain
IS - 8
ER -