Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes

The implementation of neural stem cell lines as a source material for brain tissue transplants is currently limited by the ability to induce specific neurochemical phenotypes in these cells. Here, we show that coordinated ind uction of a ventral mesencephalic dopaminergic phenotype in an immortalized multipotent neural stem cell line can be achieved in vitro. This process r equires both the overexpression of the nuclear receptor Nurr1 and factors d erived from local type 1 astrocytes. Over 80% of cells obtained by this met hod demonstrate a phenotype indistinguishable from that of endogenous dopam inergic neurons. Moreover, this procedure yields an unlimited number of cel ls that can engraft in vivo and that may constitute a useful source materia l for neuronal replacement in Parkinson's disease.