EFFECT OF OXYGEN TENSION ON THE PROLIFERATION AND THE DIFFERENTIATION OF MOUSE EMBRYONIC STEM CELLS

摘要

Embryonic stem (ES) cell is a highly expected candidate for the cell source of regenerative medicine, because ES cells retain their toti-potency capacity and are able to generate cells of all lineages (Daley et al., 2003; Odorico et al., 2001). However, the technology that controls proliferation and differentiation of ES cells in vitro is not established yet. For the self-renewal proliferation, ES cells must be in an undifferentiated state. ES cells can remain in the undifferentiated state in the presence of embryonic fibroblast feeder cells and/or leukemia inhibitory factor (LIF). There is a contrastive relation between proliferation and differentiation of ES cells. Removing the feeder cells and LIF from the ES cell culture, ES cells spontaneouslydifferentiate and chaotically generate various cell types, while the proliferation is suppressed. Strategies to control in vitro differentiation of ES cells basically consist of embryoid body (EB) formation, addition of extracellular signals (growth factors), nutrient restriction, engineered expression of master genes, and etc. (Soria, 2001). Generally oxygen is considered to play an important role in the cell culture because oxygen is needed to metabolize nutrients. Therefore, oxygen restriction wouldresult in cessation of proliferation and the initiation of cell differentiation.