Induction of neuronal differentiation of stem cell or cancer cell with VHL-gene transfer and neuronal regeneration using the transferred cells

点击翻译按钮获取中文摘要

With transductions of wild-type VHL (von Hippel-Lindau) gene, mutated-type VHL gene, and anti-sense VHL gene, we showed VHL protein had induction ability of neuronal differentiation in neural progenitor cells and neuroblastoma cells. NPCs may provide dopaminergic neurons for the treatment of Parkinson's disease (PD). However, transplantation of NPCs into the striatum by current methods has had limited success. It is possible to reverse the symptoms of PD in model rats but difficult to reverse them in humans because the number of dopaminergic neurons generated from NPCs is small (less than 1000 cells). We transduced VHL gene into NPCs isolated from embryonic rat brain. The NPCs with the trunsduced VHL gene efficiently differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro. NPCs with the trunsduced VHL gene, which were labeled in advance with bromodeoxyuridine, were transplanted into the striatum of a rat model of PD. Numerous bromodeoxyuridine-TH double-labeled cells were seen close to the transplant site, showing that the transplanted cells efficiently generated new dopaminergic neurons within he host striatum. Moreover, all of the animals with NPCs with VHL showed a remarkable decrease in apomorphine-induced rotations. These findings show that NPCs with the VHL gene can efficiently generate dopaminergic neurons and that sufficient a number of dopaminergic neurons (more than 20,000 cells) can develop from to reverse the symptoms of PD in humans. VHL gene transduction provides a new therapeutic approach for treatment of PD.