Properties of cortical precursor cells cultured long term are similar to those of precursors at later developmental stages

In vitro cultures of neural precursor cells are useful experimental tools for studies on the mechanisms of brain development, as well as for generating renewable sources in cell therapy for neurodegenerative disorders. The systematic characterization of cultured neural precursors is a prerequisite for obtaining basic information on brain development. Here, we examine the cell survival, proliferation, and differentiation potential of cultured neural precursors from different embryonic ages and those of the precursors expanded in vitro for different periods of time. Precursor cells were isolated at rat embryonic days 14 (E14) and 19 (E19) and cultured in the presence of a mitogen basic fibroblast growth factor (bFGF). The numbers of TUNEL+ and BrdU+ cells in E19 cortical precursor cultures were significantly lower than those in E14 cultures, indicating that the programmed cell death and proliferation potential of neural precursors are reduced during the progression of brain development. E14 cells tended to differentiate into neurons, and E19 cells into astrocytes. To determine whether the intrinsic properties of neural precursors are similarly altered during in vitro culture, E14 precursor cells were expanded for different periods. Precursor cells expanded for longer periods displayed lower apoptotic and proliferation indices, as well as astrogenic developmental potential. Clonal analysis data confirmed the transition of precursor differentiation potential from neurogenic to astrogenic over the culture period. Our findings collectively suggest that neural precursor cells undergo time-dependent changes in properties via an intrinsic program, both in vivo and in vitro. (C) 2004 Elsevier B.V. All rights reserved.