Hematopoietic islands and blood cell lineages
Hematopoietic cells in the red bone marrow are not scattered randomly, but form specialized colonies called islands. The bulk of these consist of maturing cells (class V). Practically all lineages of hematopoiesis are represented here.
Erythroid lineage Erythrocyte maturation is accompanied by a decrease in cell size and a change in cytoplasm color from blue to pink:
- Proerythroblasts (class IV) — the largest cells with a basophilic nucleus.
- Basophilic erythroblasts (class V) — blue nucleus and cytoplasm.
- Polychromatophilic erythroblasts — cytoplasm becomes grayish-pink due to hemoglobin accumulation and the presence of residual ribosomes.
- Orthochromatic erythroblasts — small cells with pink cytoplasm and a small pyknotic nucleus.
- Reticulocytes and erythrocytes (class VI) — post-cellular structures devoid of a nucleus.
Granulocytopoietic lineage It is divided into neutrophilic, eosinophilic, and basophilic lines. The process begins with myeloblasts (rarely seen). At the promyelocyte stage, primary (azurophilic) granulation appears. A key stage is myelocytes, when secondary (specific) granulation forms in a cell with a rounded nucleus. Next, the nucleus becomes kidney-shaped (metamyelocytes or band forms), stretches into a horseshoe (band neutrophils), and finally segments (segmented granulocytes).
Thrombopoietic lineage Distinguished by the presence of giant polyploid cells — megakaryocytes. They have extensive oxyphilic cytoplasm and are in close contact with blood capillaries. Megakaryocyte processes penetrate directly into the vessel lumen, where platelets are separated from them via clasmatosis.
Stromal component and microenvironment
The stroma creates a three-dimensional framework and the necessary conditions for hematopoiesis. It is represented by reticular tissue and specialized cells:
- Reticular cells: branched elements producing reticular fibers (type III collagen) and amorphous ground substance. They also secrete factors regulating hematopoiesis.
- Osteogenic cells: localized within the endosteum (stem cells of bone and cartilage tissue). They release factors that stimulate the proliferation and differentiation of hematopoietic cells.
- Adventitial cells: poorly differentiated fibroblastic cells covering the sinusoids from the outside. Under the influence of erythropoietin, they are capable of contracting, facilitating the exit of blood cells into the bloodstream.
- Adipocytes (fat cells): contain a large fat droplet that displaces the nucleus to the periphery. They provide local energy supply and the production of hemopoietins. It is important to note that the fat reserves of these cells are not depleted during general starvation.
Macrophage lineage
Red bone marrow macrophages develop from blood monocytes and are divided into three functional varieties:
- Typical macrophages: rich in lysosomes and phagosomes. They utilize foreign agents and hematopoiesis "waste" (such as nuclei extruded from orthochromatic erythroblasts), and also secrete growth factors.
- Nurse cells: located in the center of erythroblastic islands. Their main task is to capture iron ions ($Fe^{2+}$) from the blood and transfer them to developing erythroblasts for hemoglobin synthesis. They also secrete erythropoietin.
- Osteoclasts: multinucleated cells formed by the fusion of monocytes. They are localized in the endosteum and are responsible for bone matrix lysis during bone trabeculae remodeling.
Vascular system
Blood supply ensures trophism and the exit of mature formed elements into the blood. Lymphatic vessels are absent in the red bone marrow.
The vascular bed includes narrow capillaries (responsible only for nutrition) and sinusoidal capillaries (venous sinuses). Sinuses are wide, thin-walled vessels whose endothelium and basement membrane feature slit-like pores.
Functions of sinuses:
- Selective migration: only mature cells enter the bloodstream, recognized by the endothelium via specific surface glycoproteins.
- Maturation: the maturation of erythrocytes is completed within the sinus lumen.
- Regulation: endothelial cells secrete factors that stimulate hematopoiesis.
Blood outflow proceeds from capillaries into the central sinus, then into efferent veins penetrating the bone, and further into periosteal vessels.
Bone marrow histology slides
The study of red bone marrow is carried out on two types of preparations, each with its own characteristics:
- Bone marrow section (hematoxylin and eosin staining): Most commonly prepared from the head of a mouse embryo. The tissue is located between forming bone trabeculae. It appears as a dense accumulation of cells with dark purple nuclei. In cross-section, individual stages of hematopoiesis are difficult to distinguish, but giant megakaryocytes, wide sinusoidal capillaries with flat endothelium, and light pink reticular cells are clearly visible. It is important not to confuse bone marrow with surrounding embryonic tissues (muscles, glands, organ primordia).
- Bone marrow smear (Azure II and eosin staining): Unlike the section, cells lie loosely. Surrounding tissues are absent here, with only hematopoietic elements present. This technique allows for a detailed examination of cellular morphology and precise diagnosis of maturation stages (e.g., distinguishing a basophilic erythroblast from an orthochromatic one).
Briefly: answers to topical questions
What classes of blood-forming cells are distinguished in the modern scheme of hematopoiesis?
In the modern scheme of postembryonic hematopoiesis, 6 hierarchical classes of cells are distinguished.
- Class I — blood stem cells (HSC, pluripotent).
- Class II — hemopoietic progenitor cells (partially determined).
- Class III — unipotent progenitor cells (committed, programmed for a single cell lineage).
- Class IV — blasts (the first morphologically recognizable cells).
- Class V — maturing cells (undergoing differentiation stages).
- Class VI — mature blood formed elements.
What cytokines and growth factors regulate hematopoiesis in the bone marrow?
Hematopoiesis is regulated by a complex of humoral stimulators (hemopoietins) and inhibitors. The main groups of stimulating factors:
- Colony-stimulating factors — determine the direction of differentiation of early stages. These include multi-CSF, erythropoietin, thrombopoietin, granulocyte CSF, and thymopoietins.
- Interleukins — regulate the activity and proliferation of differentiated cells. They include IL-1 through IL-7 (with IL-3 being essential at all stages).
Inhibition of hematopoiesis is carried out by specific inhibitors (chalones), tissue hormones (prostaglandins, interferon), and glucocorticoids.
Where is red bone marrow located in an adult?
In an adult, red bone marrow is located in the intertrabecular spaces of spongy bone tissue.
Spongy bone tissue is found in the inner parts of flat and short bones, as well as in the epiphyses of long bones. In the diaphyses of long bones in adults, hematopoietic tissue is replaced by adipose tissue with the formation of yellow bone marrow. The total mass of red bone marrow in an adult is 3.0–3.5 kg.
Rule of erythropoiesis: "From blue to pink." The color of the cytoplasm changes as blue ribosomes are lost and pink hemoglobin accumulates (basophilic → polychromatophilic → orthochromatic).
Class and exam questions
This is the result of combined staining: residual ribosomes in the cytoplasm impart a blue color, while newly accumulating hemoglobin imparts a pink color.
This is the result of combined staining: residual ribosomes in the cytoplasm impart a blue color, while newly accumulating hemoglobin imparts a pink color.
At which stage of granulocytopoiesis does specific granulation appear?
Specific (neutrophilic, eosinophilic, or basophilic) granulation first appears at the myelocyte stage (class V cells).
How do mature cells know it is time to enter the bloodstream?
The process is controlled by the endothelium of sinusoidal capillaries. It recognizes mature formed elements by specific surface glycoproteins on their membrane, ensuring selective migration.
What else to study on this topic
- Lymphocyte-like elements: stem cell reserve and B-lymphocyte maturation
- Immunoglobulin gene rearrangement process
- Mechanism of iron ion transfer by nurse cells
- Interaction between the endosteum and hematopoietic tissue
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