The structure of the bone marrow

A trephine biopsy allows a two-dimensional view of the bone marrow down the light microscope (Fig 1.2). Haematopoietic cells of varying lineage and maturity are packed between fat spaces and bony trabeculae. Ultrastructural studies reveal clusters of haematopoietic cells surrounding vascular sinuses which allow eventual discharge of mature cells into the blood. Different lineages are compartmentalised; for example, the most immature myeloid precursors lie deep in the marrow parenchyma while more mature forms migrate towards the sinus wall. Lymphocytes tend to surround small radial arteries while erythrocytes form islands around the sinus walls.

Blood precursor cells in the marrow exist in close proximity to stromal cells. Stromal cells are those cells which do not mature into the three main types of peripheral blood cells – thus they include macrophages, fat cells, endothelial cells and reticulum cells.

Immature blood cells are attached to these stromal cells by multiple cellular adhesion molecules (e.g. fibronectin and collagen). Adhesive molecules have specific receptors on stromal and haematopoietic cells. As blood cells mature, the receptors down-regulate and the cells become less adherent and commence the journey through the sinus wall and into the bloodstream.

Haematopoiesis: the stem cell hierarchy

Haematopoiesis means the formation of blood. A number of transcription factors (e.g. GATA-1, MLL) are critical both for stem cell formation and function and lineage-specific differentiation.

The first adult haematopoietic stem cells (HSCs) are generated in the aorto-gonad-mesonephros (AGM) region of the embryo. The classical hierarchy diagram (Fig 1.3