To harness stem cells by manipulation of energetic metabolism

The maintenance of the primitive Hematopoietic Stem Cells (HSC) in course of ex vivo expansion is a critical point to preserve the long-term reconstituting capacity of a hematopoietic graft. On the basis of the numerous experimental results, the maintenance of primitive HSC is related to their specific metabolic profile shifted towards the anaerobiosis. Hence, in addition to the exposition of the cultures to more appropriate, physiologically low O₂ concentrations (usually misleadingly termed "hypoxia"), a specter of "hypoxia-mimicking" factors (cytokines, growth factors, receptor-ligands, antioxidants) can be applied to maintain this specific metabolic profile enabling an appropriate genetic and epigenetic regulation. Some factors already proved to be able to achieve this goal and "hypoxia-mimicking" ex vivo cultures were already used to produce cells for clinical trials. In this article we are discussing the approaches aimed to amplify and/or to condition the HSC, based on the manipulation of energetic metabolism properties.