Individual fates of mesenchymal stem cells in vitro

By simulation studies, we provide detailed insight into the kinetics of MSC organisation. Monitoring the fates of individual cells in high and low oxygen culture, we calculated the average transition times of individual cells into stem cell and differentiated states. We predict that at low oxygen the heterogeneity of a MSC population with respect to differentiation regenerates from any selected subpopulation in about two days. At high oxygen, regeneration becomes substantially slowed down. Simulation results on the composition of the functional stem cell pool of MSC populations suggest that most of the cells that constitute this pool originate from more differentiated cells.Individual cell-based models are well-suited to provide quantitative predictions on essential features of the spatio-temporal organisation of MSC in vitro. Our predictions on MSC plasticity and its dependence on the environment motivate a number of in vitro experiments for validation. They may contribute to a better understanding of MSC organisation in vitro, including features of clonal expansion, environmental adaptation and stem cell ageing.The generation and maintenance of replenishing tissues relies on an appropriately regulated balance between self-renewal and differentiation within a relatively small population of adult stem cells. According to the common stem cell paradigm this balance can be explained assuming a strict differentiation hierarchy and irreversible fate decisions [1,2]. However, the organisation of stem cell populations is strongly influenced by environmental factors such as specific cell-cell interactions, growth factor and oxygen supply, as well as the geometry and mechanical properties of the local environment [3,4]. Accordingly, it has been suggested that stemness represents a particular regulatory cell state rather than an entity and that this state may be approached in principle by any cell [5,6]. Supporting these ideas, recent experimental results in hematopoietic sys