Adult stem cell differentiation: what does it mean?

The very property that puts adult stem cells in high demand, their ability to differentiate into mature cells with specialized functions, is a barrier to their expansion in culture. In many cases, tissue cell differentiation programs conclude with terminal division arrest and, eventually, cell death. Therefore, propagation and expansion of many types of normal mature cells in sufficient quantities for therapeutic applications is impractical. A method to expand adult somatic stem cells (SSCs), which are programmed for indefinite division, would provide a solution to this problem. After expanding SSCs to the quantities required, subsequent cell differentiation could yield large numbers of needed mature functional cells. A general approach is described for clonal expansion of adult SSCs. The method is based on suppression of asymmetric cell kinetics ("SACK"), a strategy that limits stem cell differentiation. As a first proof of principle, the SACK method was recently used to derive hepatic stem cells from adult rat liver. In addition to providing a potential method for routine expansion of adult SSCs from diverse mammalian tissues, the success of these initial studies elucidates the nature of "stem cell differentiation" in vitro and in vivo.