The Size of Human Mesenchymal Tissue Stem Cell Turnover Units is a Major Determinant for Maintaining High Stem Cell Fractions With Serial Culture Expansion.

Recently, we used kinetic stem cell (KSC) counting to show that the stability of the stem cell fraction (SCF) during serial culture expansion of human oral alveolar bone mesenchymal tissue cell (MTC) preparations varied significantly among patient donors. Whereas some patient donor samples' SCFs declined rapidly, others showed a moderate decrease; and still others had highly stable SCFs during serial culture expansion. Defining the cell kinetics basis for these differences in SCF stability could lead to effective solutions for the problem of loss of mesenchymal stem cell (MSC) function when MTC preparations are expanded for research and clinical applications. Using KSC counting, we show that greater SCF stability is associated with smaller stem cell turnover units, which reduce the SCF by cell dilution. This finding confirms earlier evidence and proposals that, by limiting the production and proliferation of committed progenitor cells, more effective expansion of tissue stem cells, such as MSCs, can be achieved. Because of the universal nature of tissue stem cell turnover units and the continuation of their basic cell kinetics programs in in vitro cell culture, the effects defined herein are predicted to apply to other types of human tissue stem cells of interest for stem cell medicine.