Stem Cells and Haemopoiesis

Haemopoietic stem cells (HSCs) are the foundation of the adult blood system and sustain the lifelong production of all blood lineages. These rare cells are generally defined by their ability to self-renew through a process of asymmetric cell division, the outcome of which is an HSC and a differentiating cell. In health, HSCs provide homeostatic maintenance of the system through their ability to differentiate and generate the hundreds of millions of erythrocytes and leukocytes needed each day. In trauma and physiological stress, HSCs ensure the replacement of the lost or damaged blood cells. The tight regulation of HSC self-renewal ensures the appropriate balance of blood cell production. Perturbation of this regulation and unchecked growth of HSCs and/or immature blood cells results in leukaemia. Over the last 50 years, great success has been achieved with bone marrow transplantation as a stem cell regenerative therapy. However, insufficient numbers of HSCs are still a major constraint in clinical applications. As the pivotal cells in this essential tissue, HSCs are the focus of intense research to 1) further our understanding of their normal behaviour and the basis of their dysfunction in haemopoietic disease and leukaemia and, 2) to provide insights for new strategies for improved and patient-specific stem cell therapies. This chapter provides current and historical information on the organization of the adult haemopoietic cell differentiation hierarchy, the ontogeny of HSCs, the stromal microenvironment supporting these cells, and the molecular mechanisms involved in the regulation of HSCs.