ABSTRACT
I. INTRODUCTION Hematopoiesis is a complex process in which hematopoietic stem cells can self-replicate but also differentiate into myeloid and lymphoid lineage-committed progenitors. These committed progenitors undergo further multiplications before they terminally differentiate into mature blood elements. The process of myelopoiesis, B lymphopoiesis, T lymphopoiesis, and natural killer cell generation occurs in close proximity with a permissive microenvironment, which in adult life is provided in the bone marrow (Fig 1). The factors responsible and necessary for an orderly hematopoietic process, in which progenitors remain either quiescent or proliferate, differentiate, and mature are not yet understood. The marrow microenvironment is a complex organ in which so-termed stromal cells are responsible for providing most, if not all, factors required for the orderly development of the stem cell. Stromal cells are both mesenchymal and hematopoietic in origin, and they include osteoblasts, fibroblasts, adipocytes, myocytes, endothelial cells, dendritic cells, and macrophages. These cells are responsible for the production and deposition of a complex extracellular matrix (ECM) and the local production and concentration of hematopoietic cytok-
Figure 1 Schematic representation of stem and progenitor cell interactions with the marrow microenvironment. Hemopoietic stem and progenitor cells are localized within the bone marrow microenvironment where they are subject to interactions with growth-promoting and growth-inhibitory cytokines as well as with extracellular matrix components and stromal cell adhesive ligands.
