Lack of communication rusts and ages stem cells

Life-long hematopoietic demands are filled by a pool of hematopoietic stem cells (HSC) with self-renewal and multipotential differentiation ability. Generation of reactive oxygen species (ROS) at low and moderate levels is required for HSC activity. However, a sustained, abnormal increase in ROS production occurs under aging and genotoxic stress, which inhibits HSC self-renewal and induces HSC senescence and hematopoietic dysfunction. How ROS levels are restored in HSC, and ROS-induced DNA damage prevented is not well understood, but both HSC autonomous and non-cell autonomous are likely at play. In the bone marrow (BM), HSC activity requires a nurturing hematopoietic microenvironment (HM). While multiple mechanisms are arguably responsible for the control of the HM on HSC activity, all of them can be sorted into three categories: cytokine receptor-ligand interaction, the interaction of adhesion molecules on hematopoietic cells with BM stromal cells or the extracellular matrix, or direct cellto-cell communication between stromal cells and HSC. In patients undergoing cancer therapy, the functional reserve of normal BM HSC largely determines the hematological toxicity associated with the use of cytostatic drugs and significantly influences their morbi-mortality. The functional reserve of HSC depends on the number of cells and the intrinsic ability of HSC to selfrenew and differentiate in an uncompromised microenvironment and is controlled by a number of modifier genes. These factors often result in a heterogenous, Lack of communication rusts and ages stem cells