In vitro generation and transplantation of precursor-derived human dopamine neurons

The use of in vitro expanded human CNS precursors has the potential to over come some of the ethical, logistic and technical problems of fetal tissue t ransplantation in Parkinson disease. Cultured rat mesencephalic precursors proliferate in response to bFGF and upon mitogen withdrawal, differentiate into functional dopamine neurons that alleviate motor symptoms in Parkinson ian rats (Studer et al. [1998] Nat. Neurosci. 1:290-295). The successful cl inical application of CNS precursor technology in Parkinson disease will de pend on the efficient in vitro generation of human dopaminergic neurons. We demonstrate that human dopamine neurons can be generated from both midbrai n and cortical precursors. Transplantation of midbrain precursor-derived do pamine neurons into Parkinsonian rats resulted in grafts rich in tyrosine h ydroxylase positive neurons 6 weeks after transplantation. No surviving tyr osine hydroxylase positive neurons could be detected when dopamine neurons derived from cortical precursors were grafted. Our data demonstrate in vitr o derivation of human dopamine neurons from expanded CNS precursors and enc ourage further studies that systematically address in vivo function and cli nical potential. (C) 2001 Wiley-Liss, Inc.