Oxygenation level as a factor in stem cell maintenance

This article will describe the decade-long genesis of a research project and review its main results. These results point to oxygenation level being a physiological regulator of haematopoietic stem cell maintenance because: (1) very low oxygen concentrations (~0.1%) enable the preservation of the quiescent (G0) stem cell pool; (2) low oxygen concentrations (~1%) are compatible with the proliferation of primitive stem cells but inhibit their differentiation, i.e. enable their self-renewal; (3) moderately low oxygen concentrations (~3%) allow a balance between differentiation and self-renewal, permitting the simultaneous amplification of progenitors and the maintenance of stem cell activity; and (4) very high oxygen concentrations, like those in the air (20-21%), enhance the differentiation of primitive stem cells, abrogating their self-renewal capacity. In spite of the fact that these oxygen concentrations do not exist in tissues in vivo, they are usually used for in vitro cell growth. These results represent a new insight into the regulatory mechanisms of haematopoiesis. In that light they are cited in top biomedical literature and accepted as being relevant to the development of tissue and cell engineering. In that respect, we are working on the adaptation of culture oxygenation to improve existent ex vivo expansion techniques. We are also trying to improve the techniques of ex vivo production of red blood cells in the same manner. Our other ongoing research projects are directed at improving the conservation of stem cells at low temperatures (but above freezing point) within a liquid medium, by decreasing oxygen and increasing CO2 concentrations.