Overview of Hematopoiesis: Blood Cell Formation Process

Blood Cell Formation

The process of hematopoiesis commences the formation of blood cells; that is, platelets, leucocytes (white blood cells), and erythrocytes (red blood cells). Blood cell formation occurs in the red bone marrow when the pluripotential stem cell differentiates into the myeloid mltipotential cell and lymphoid mulitpotential cell.

Red Blood Cells Formation

Erythrocytes have a short life of 120 days. Moreover, their inability to mitotically divide and numerate surpasses their control to enable cell growth and repair. In this regard, red blood cells endure the process of erythropoiesis, which facilitates the replacement of old ruptured cells with new cells.

Firstly, the red blood cells are produced in the yolk sac during intrauterine development. They are further formed in the developing spleen during the third month of gestation until the bone marrow is formed at seven months. Once the kidney detects low oxygen levels in the body, it releases the hormone erythropoietin that enhances the development of the hemocytoblast to an erythrocyte through differentiation. That is to say, the hemocytoblast differentiates to a nucleated erythroblast, which extrudes their nucleus and cell organelles to facilitate room for hemoglobin concentration (Eaves, 2015). This further differentiates into a reticulocyte, an immature red blood cell with organelle remnants. Once matured, the erythrocytes are released into the capillaries to increase the blood oxygen levels thus the kidneys reduce the release of the erythropoietin hormone hence red cell production decreases (Palis, 2016).

Formation of Platelets

Platelets are formed and released into the cardiovascular system from their precursor cells, megakaryocytes in the bone marrow. In addition, the thrombopoietin hormone, produced from the liver and kidneys regulate platelet production. The normal platelet count is about 150,000 to 450,000 per microliter of blood. Moreover, the average adult produces 1011 platelets per day to preserve the platelet count. On this note, platelets constitute the most abundant cell type after erythrocytes (Palis, 2016).

During Thrombopoiesis, a process of thrombopoietin regulation, the committed hematopoietic stem cell differentiates into a megakaryocyte through transcription (Twomey et al., 2018). The cell increases in size between 50 and 100 um and endures DNA ploidy levels that facilitate RNA, organelle, and protein accumulation for packaging into platelets. The megakaryocytes then drift to the sinusoidal blood vessels in the vascular system where pro-platelets are formed. Finally, anucleate fragments of pro-platelets divide into pre-platelets and barbell-shaped platelets that are then formed into single platelets within the blood stream.

Formation of T-lymphocyte

The T-cells develop from a lymphoid progenitor in the bone marrow that also produces B lymphocytes. Nevertheless, the progenitor later migrates to the thymus where most maturation of the T lymphocytes occurs. The T-cells in the thymus endure a series of differential stages presented by the status of the T-cell receptor genes and changes in their cell surface proteins. The principal stages of T-lymphocytes include, α:β and γ:δ. These mature and become distinct functional sets of CD8 and CD4 T-cells (Janeway CA Jr, Travers P, Walport M, 2001).

Platelet function in Hemostasis

The haemostasis process in platelets can be subdivided into three events, that is, primary haemostasis, secondary hemostasis, and fibrinolysis. The primary hemostasis enhances the physiological process that inhibits bleeding during injury while maintaining normal blood flow by forming a platelet plug and initiating vasoconstriction, secondary hemostasis ensures the deposition of fibrin, and fibrinolysis or coagulation facilitates the breakdown of blood clots during wound healing.

Normally, platelets circulate at the peripheral of vascular walls. Furthermore, inhibitory factors such as the endothelial monolayer, nitric oxide, and PGI2 prevent the cells untimely activation processes (Twomey et al., 2018). Nevertheless, platelets become active once the endothelial layer lining is disrupted and exposes the underlying sub-endothelial matrix.

During vascular injury for example when one falls and grazes the knee, the blood vessels damage and expose both the sub-endothelial matrix and proaggregatory proteins like the von Willebrand factor (vWF) and collagen. vWF associates with a glycoprotein complex (GPIb-V-IX) to slow down the movement of platelets thus enabling the cells to bind with the collagen through GPVI. The association of collagen to GPVI stimulates an intracellular signaling flow that involves tyrosine kinase-mediated compliments. On the other hand, the promotion of platelet activities initiates a conformational change of integrin αIIbβ3 hence enable the formation of the platelet plug with fibrinogen. The process also stimulates the secretion of adenosine diphosphate (ADP) and thromboxane A2 synthesis. Prothrombin is cleaved into thrombin, which activates more platelets thus stimulating the formation of the platelet plug to scab the damaged vessels while the blood vessels constrict to inhibit bleeding. Notably, engagements of the coagulation processes promote fibrin mesh, which compresses and strengthens the thrombus. (Vallance et al., 2017).

References

• Eaves, C. J. (2015). Hematopoietic Stem Cells: Concepts, Definitions, and The New Reality. Blood, 125(17), 2605-2613.
• Janeway CA Jr, Travers P, Walport M. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Generation of Lymphocytes in Bone Marrow and Thymus. Available from: https://www.ncbi.nlm.nih.gov/books/NBK27123/
• Palis, J. (2016). Hematopoietic Stem Cell‐Independent Hematopoiesis: Emergence of Erythroid, Megakaryocyte, and Myeloid Potential in the Mammalian Embryo. FEBS letters, 590(22), 3965-3974.
• Twomey, L., Wallace, R. G., Cummins, P. M., Degryse, B., Sheridan, S., Harrison, M., & Murphy, R. P. (2018). Platelets: From Formation to Function. In Homeostasis-An Integrated Vision. IntechOpen.
• Vallance, T. M., Zeuner, M. T., Williams, H. F., Widera, D., & Vaiyapuri, S. (2017). Toll-Like Receptor 4 Signalling and Its Impact on Platelet Function, Thrombosis, and Hemostasis. Mediators of inflammation, 2017.