Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in parkinsonian rats.
We show that human embryonic stem cell-derived dopaminergic neurons survived transplantation to the neurotoxin 6-hydroxydopamine-lesioned rat striatum and, in combination with the cells newly differentiated from their progenitors, contributed to locomotive function recovery at 5 months. The animal behavioral improvement was correlated with the dopamine neurons present in the graft. Although the donor cells contained forebrain and midbrain dopamine neurons, the dopamine neurons present in the graft mainly exhibited a midbrain, or nigra, phenotype, suggesting the importance of midbrain dopamine neurons in functional repair. Furthermore, progenies of grafted cells were neurons and glia with greatly diminished mitotic activity by 5 months. Thus, the in vitro-produced human dopamine neurons can functionally engraft in the brain.
Yang
Dali
D
Department of Anatomy, School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Zhang
Zhi-Jian
ZJ
Oldenburg
Michael
M
Ayala
Melvin
M
Zhang
Su-Chun
SC
D000818:Animals; D001921:Brain / Q000601:surgery; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005260:Female; D006085:Graft Survival; D006801:Humans; D008636:Mesencephalon / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D020734:Parkinsonian Disorders / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function
D004298:Dopamine