Mathematical models for the proliferation of neural stem/progenitor cells in clonogenic culture

Neurospheres are free-floating heterogeneous spheroid structures maintained in culture and have been used for in vitro expansion of neural stem/progenitor cells. But the growth characteristics and proliferation kinetics of cell population in neurospheres are poorly understood. Using clonogenic culture and immunocytochemistry, we observed the growth dynamics of cell populations in neurospheres and identified key parameters relating to the growth dynamics of cells in neurospheres, including the fraction of dividing cells, cell cycle duration, time delay of first division, and survival rate of cells. Based on these parameters, we established two mathematical models that describe kinetic features of neural stem/progenitor cells under clonogenic conditions. These models provide a powerful tool to explain and predict the experimental outcome and clarify the cell growth characteristics of neural stem/progenitor cells.