Wagner J, Akerud P, Castro D S, Holm P C, Canals J M, Snyder E Y, Perlmann T, Arenas E
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Nat Biotechnol. 1999 Jul;17(7):653-9. doi: 10.1038/10862.
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 induction of a ventral mesencephalic dopaminergic phenotype in an immortalized multipotent neural stem cell line can be achieved in vitro. This process requires both the overexpression of the nuclear receptor Nurr1 and factors derived from local type 1 astrocytes. Over 80% of cells obtained by this method demonstrate a phenotype indistinguishable from that of endogenous dopaminergic neurons. Moreover, this procedure yields an unlimited number of cells that can engraft in vivo and that may constitute a useful source material for neuronal replacement in Parkinson's disease.
目前，将神经干细胞系用作脑组织移植的源材料受到在这些细胞中诱导特定神经化学表型能力的限制。在此，我们表明在体外可实现永生化多能神经干细胞系中腹侧中脑多巴胺能表型的协同诱导。这一过程既需要核受体Nurr1的过表达，也需要源自局部1型星形胶质细胞的因子。通过这种方法获得的细胞中，超过80%表现出与内源性多巴胺能神经元无法区分的表型。此外，该程序可产生无限数量的细胞，这些细胞能够在体内移植，可能构成帕金森病神经元替代的有用源材料。
