4 - Low O2 Concentrations and the Maintenance of Stem Cells Ex Vivo

Abstract

After the historic review concerning the ex vivo culture of living cells and their oxygenation, in this chapter the available data on embryonic and several adult stem/progenitor cells systems were analyzed. After taking into consideration (1) the heterogeneity of cell populations studied, (2) type of stimulation of culture, and (3) application of a “correction” of the viewpoint (i.e., considering the atmospheric O2 concentrations as not physiologic but the increased ones), it can be concluded that the O2 concentration to which the culture is exposed has a great impact on the self-renewal, commitment, and differentiation processes. If properly stimulated, the primitive stem cell subsets respond to the physiologically relevant O2 concentrations by maintaining their proliferative capacities, either setting the self-renewal/commitment balance toward self-renewal or by maintaining the quiescent state. Increase in O2 concentration from the lowest values (corresponding to the ones in the in vivo stem cells niche) toward the intermediary physiologically relevant values is premising for the commitment of stem cells. Stem cell maintenance, decline, or total exhaustion is a function of actual oxygenation level. The response of committed progenitors is rather different: the very low O2 concentrations induce the quiescence of these cells, the intermediate O2 concentrations maintain the proliferative progenitors with a decreased differentiation rate, and the higher ones enhance the differentiation process. Some committed progenitors whose differentiation specifically demands reduced oxygenation (i.e. endothelial) are stimulated to differentiate in low O2 concentrations. Altogether the ex vivo data suggest that O2 requirement and sensitivity to low oxygen condition depend on the developmental stage of stem cells and the way and level of commitment of progenitor cells.