Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity.
We previously identified a stromal cell-derived inducing activity (SDIA), which induces differentiation of neural cells, including midbrain tyrosine hydroxylase-positive (TH(+)) dopaminergic neurons, from mouse embryonic stem cells. We report here that SDIA induces efficient neural differentiation also in primate embryonic stem cells. Induced neurons contain TH(+) neurons at a frequency of 35% and produce a significant amount of dopamine. Interestingly, differentiation of TH(+) neurons from undifferentiated embryonic cells occurs much faster in vitro (10 days) than it does in the embryo (approximately 5 weeks). In addition, 8% of the colonies contain large patches of Pax6(+)-pigmented epithelium of the retina. The SDIA method provides an unlimited source of primate cells for the study of pathogenesis, drug development, and transplantation in degenerative diseases such as Parkinson's disease and retinitis pigmentosa.
Kawasaki
Hiroshi
H
Department of Medical Embryology and Neurobiology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Suemori
Hirofumi
H
Mizuseki
Kenji
K
Watanabe
Kiichi
K
Urano
Fumi
F
Ichinose
Hiroshi
H
Haruta
Masatoshi
M
Takahashi
Masayo
M
Yoshikawa
Kanako
K
Nishikawa
Shin-Ichi
S
Nakatsuji
Norio
N
Sasai
Yoshiki
Y
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D017690:Cell Transplantation; D002478:Cells, Cultured; D004298:Dopamine / Q000032:analysis*; D004847:Epithelial Cells / Q000166:cytology*; D008252:Macaca fascicularis; D051379:Mice; D016513:Mice, SCID; D019006:Neural Cell Adhesion Molecules / Q000032:analysis; D009474:Neurons / Q000166:cytology*; D011323:Primates; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D017154:Stromal Cells / Q000166:cytology*; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; D019006:Neural Cell Adhesion Molecules; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine