Hemopoiesis

Department Of General Histology

Introduction• Mature blood cells have a relatively short life span and must be

continuously replaced with stem cell progeny produced in the hemopoietic (Gr. haima, blood, + poiesis, a making) organs. In the earliest phase of human embryogenesis, blood cells arise from the yolk sac mesoderm. In the second trimester, hemopoiesis (also called hematopoiesis) occurs primarily in the developing liver, with the spleen also playing a role. Skeletal elements begin to ossify and bone marrow develops in their medullary cavities, so that, in the third trimester, bone marrow increasingly becomes the major hemopoietic organ.

• After birth and on into childhood, erythrocytes, granulocytes, monocytes, and platelets are derived from stem cells located in bone marrow. The origin and maturation of these cells are termed, respectively, erythropoiesis (Gr. erythros, red, + poiesis), granulopoiesis, monocytopoiesis, and thrombocytopoiesis. Development of the major types of lymphocytes by lymphopoiesis occurs in the marrow and in the lymphoid organs to which precursor cells migrate, as discussed in Chapter 14.

• Before reaching maturity and being released into the circulation, blood cells go through specific stages of differentiation and maturation. Because these processes are continuous, cells with characteristics that lie between the various stages are frequently encountered in smears of blood or bone marrow.

Main characteristics of five hemopoietic growth factors (colony-stimulating factors, CSF).

Red bone marrow (active in hemopoiesis)Red bone marrow contains adipocytes but is also active in hemopoiesis, with several cell lineages usually present. It can be examined histologically in sections of bones or in biopsies, but its cells can also be studied in smears. Marrow consists of capillary sinusoids running through a stroma of specialized, fibroblastic reticular cells and an ECM meshwork. Reticular cells secrete various colony-stimulating factors and the stroma forms the microenvironment for hemopoietic stem cell maintenance, proliferation, and differentiation. This section of red bone marrow shows some of its components. Sinusoid capillaries (S) containing erythrocytes are surrounded by stroma containing adipocytes (A) and islands or cords (C) of hemopoietic cells. Sinusoidal endothelial cells (one nucleus at E) are very thin. Most reticular cells and cells of the hemopoietic lineages are difficult to identify with certainty in routinely stained sections of marrow.

Sinusoidal endothelium in active marrow

Summary of erythrocyte maturation

Erythropoiesis: Major erythrocyte precursors

(a): Micrographs showing a very large and scarce proerythro-blast (P), a slightly smaller basophilic erythroblast (B) with very basophilic cytoplasm, typical and late polychromatophilic erythroblasts (Pe and LPe) with both basophilic and acidophilic cytoplasmic regions, and a small orthochromatophilic erythroblast (Oe) with cytoplasm nearly like that of the mature erythrocytes in the field.

Micrograph containing reticulocytes (arrows) that have not yet completely lost the polyribosomes used to synthesize globin, as demonstrated by a stain for RNA. X1400. Brilliant cresyl blue.

Granulopoiesis: Formation of granules

Developing erythrocytes and granulocytes in marrow. Precursor cells of different

hemopoietic lineages develop side by side with some intermingling as various cell islands or cords in the bone marrow. Plastic section of red bone marrow showing mitotic figures (arrows), a plasma cell (arrowhead), and fairly distinct regions of erythropoiesis and granulopoiesis. Most immature granulocytes are in the myelocyte stage: their cytoplasm contains large, dark-stained azurophilic granules and small, less darkly stained specific granules. X400. Giemsa.

Granulopoiesis: Major granulocyte precursors.Two micrographs from smears of bone marrow showing the major cells of the neutrophilic granulocyte lineage. Typical precursor cells shown are labeled as follows: myeloblast (MB); promyelocyte (1); myelocytes (2); late myelocyte (3); metamyelocytes (4); stab or band cells (5); nearly mature segmented neutrophil (6). Some of the early stages show faint nucleoli (N). Inset: Eosinophilic myelocytes (EM) and metamytelocytes (EMm) with their specific granules having distinctly different staining. These and cells of the basophilic lineage are similar to developing neutrophils, except for their specific staining granules and lack of the stab cell form. Also seen among the erythrocytes of these marrow smears are some orthochromatophilic erythroblasts (Oe), a small lymphocyte (L), and a cell in mitosis (arrow). All X1400. Wright.

Neutrophilic myelocyteAt the myelocyte stage lysosomes (azurophilic granules) have formed and production of specific secretory granules is underway. This micrograph shows ultrastructurally a peroxidase-stained section of a neutrophilic myelocyte with cytoplasm containing both large, peroxidase-positive azurophilic granules (AG) and smaller specific granules (SG), which do not stain for peroxidase. The peroxidase reaction product is present only in mature azurophilic granules and is not seen in the rough ER (RER) or Golgi cisternae (GC), which are located around the centriole (C) near the nucleus (N).

Functional compartments of neutrophils

Megakaryoblast and megakaryocytes

Megakaryoblasts (Mb) are very large, fairly rare cells in bone marrow, with very basophilic cytoplasm. X1400. Wright.

Megakaryoblasts undergo endomitosis (DNA replication without intervening cell divisions), becoming polyploid as they differentiate into megakaryocytes (M). These cells are even larger, but with cytoplasm that is less intensely basophilic. X1400. Wright.

Micrograph section of bone marrow megakaryocyte (M) shown near sinusoids (S). X400. Giemsa. Megakaryocytes produce all the characteristic components of platelets (membrane vesicles, specific granules, marginal microtubule bundles, etc) and in a complex process extend many long, branching pseudopodia-like projections called proplatelets, from the ends of which platelets are pinched off almost fully formed.

Megakaryocyte ultrastructure

TEM analysis of a megakaryocyte during platelet formation showing a lobulated nucleus (N), numerous cytoplasmic granules (G), and an extensive system of demarcation membranes (D) through the cytoplasm. Once believed to be perforations along which platelets were shed from the cells, this membrane system is now considered a reservoir of membrane used during elongation of the numerous proplatelets which extend from the megakaryocyte surface. X10,000.

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