Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model.
Parkinson disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic (DA) neurons. ES cells are currently the most promising donor cell source for cell-replacement therapy in PD. We previously described a strong neuralizing activity present on the surface of stromal cells, named stromal cell-derived inducing activity (SDIA). In this study, we generated neurospheres composed of neural progenitors from monkey ES cells, which are capable of producing large numbers of DA neurons. We demonstrated that FGF20, preferentially expressed in the substantia nigra, acts synergistically with FGF2 to increase the number of DA neurons in ES cell-derived neurospheres. We also analyzed the effect of transplantation of DA neurons generated from monkey ES cells into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated (MPTP-treated) monkeys, a primate model for PD. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons and attenuated MPTP-induced neurological symptoms.
Takagi
Yasushi
Y
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Takahashi
Jun
J
Saiki
Hidemoto
H
Morizane
Asuka
A
Hayashi
Takuya
T
Kishi
Yo
Y
Fukuda
Hitoshi
H
Okamoto
Yo
Y
Koyanagi
Masaomi
M
Ideguchi
Makoto
M
Hayashi
Hideki
H
Imazato
Takayuki
T
Kawasaki
Hiroshi
H
Suemori
Hirofumi
H
Omachi
Shigeki
S
Iida
Hidehiko
H
Itoh
Nobuyuki
N
Nakatsuji
Norio
N
Sasai
Yoshiki
Y
Hashimoto
Nobuo
N
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D008252:Macaca fascicularis; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine