Cancer stem cells obtained from normal brain stem cells

Abstract

Current cell replacement therapy strategies include transplantation of stem cells for neurodegenerative diseases, such as Parkinson's. While ES cells besides being ethically questionable have been shown to produce malignant teratomas upon transplantation, adult stem cells have the advantage of being free of ethic concerns and hitherto were thought of not being tumorigenic. Here, we show that in vitro expansion of adult neural stem and progenitor cells harbours the risk of inducing genetic instability resulting in tumorigenic cells. We obtained stem and progenitor cells from the subventricular zone of Wistar rats and passaged these cells serially in vitro. In passage ten, cellular morphology appeared more rounded and the cells did not stop proliferating under differentiation conditions. We thus generated two cell lines with similar characteristics. Both cell lines expressed typical stem cell markers (e.g. Musashi-1, Nestin and CD133), showed multiple chromosomal aberrations and generated primitive neuroectodermal tumors when transplanted into syngenic, immunocompetent hosts. We identified the platelet derived growth factor receptor alpha as candidate for the continued proliferation of these cancer stem cell lines. Furthermore, we generated a cancer stem cell line from human hippocampal stem and progenitor cells, which expressed similar characteristics in vitro and in vivo. We conclude that adult stem cells are highly susceptible to transformation events, that in vitro expansion of adult stem cells is a risk factor for reconstructive therapy strategies and should be closely monitored for transformation of stem cells.