Fig. 1.

Emergence of MSC diversity during life span. Early in life, most, if not all, uncommitted MSC exhibit multipotential differentiation capacity, and their developmental fate is tightly controlled. In due course, additional types of mesenchymal precursors emerge as stable subpopulations. The rate of cell death is gradually increasing (MSC^dying). Other MSC accumulate various forms of damage which cannot be compensated by cellular repair (MSC^degen). Due to an age-dependent change in the activity of bioactive differentiation cues, be it their respective availability or alterations in cellular response or because of chronic, systemic inflammation, a subpopulation of uncommitted MSC becomes manifest: predetermined mesenchymal precursors (MPC). In total, only little decline of mesenchymal progenitor cell numbers is envisaged at advanced age. However, the number of truly naive, multipotential MSC steadily declines.