Ventral midbrain neural stem cells have delayed neurogenic potential in vitro

Neural stem cells (NSCs) have been the focus of an intensive effort to direct their differentiation in vitro towards desired neuronal phenotypes for cell replacement therapies. It is thought that NSCs derived from older embryos have limited neurogenic capacity and are restricted towards an astroglial fate. This idea is largely based on studies that typically analysed NSC-derived progeny following one week of in vitro differentiation. In this report, the neurogenic capacity of older ventral midbrain (VM) NSCs was assessed. When the older NSCs were differentiated for three weeks, there were significant increases in the numbers of newly born neurons at 14 and 21 days, as assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation. Therefore this study demonstrates that older NSCs retain significantly more neurogenic potential than was previously thought. These data have implications for NSC preparatory protocols and the choice of donor age for cell transplantation studies, and contributes to the understanding of NSC behaviour in vitro.