title: Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takagi
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.forename: Hidemoto
authors.initials: H
authors.lastname: Saiki
authors.forename: Asuka
authors.initials: A
authors.lastname: Morizane
authors.forename: Takuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Yo
authors.initials: Y
authors.lastname: Kishi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fukuda
authors.forename: Yo
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Masaomi
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Makoto
authors.initials: M
authors.lastname: Ideguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Imazato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Suemori
authors.forename: Shigeki
authors.initials: S
authors.lastname: Omachi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Iida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Itoh
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sasai
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hashimoto
mesh_terms: 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
chemical_list: D015415:Biomarkers; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine