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.
