Megakaryocytes are the precursor cells of platelets (blood thrombocytes). They are located in the bone marrow and are formed from pluripotent stem cells. Disorders in platelet formation lead to either thrombocythemia (uncontrolled platelet formation) or thrombocytopenia (decreased platelet formation).
What are megakaryocytes?
Megakaryocytes, as hematopoietic cells of the bone marrow, are the precursor cells of platelets. They are among the largest cells in the human body. Thus, they can reach a diameter of up to 0.1 mm. The initial cells of the megakaryocytes are the so-called megakaryoblasts, which can no longer divide by mitosis. Instead, endomitosis constantly takes place, which leads to the polyploid cell nuclei of the megakaryocytes. Megakaryocytes can thus achieve a chromosome set up to 64 times that of normal cells. The cytoplasm of megakaryoblasts is basophilic. It can be stained purple or blue by basic dyes such as methylene blue, hematoxylin, toluidine blue, or thionine. After several endomitoses, the mature megakaryocyte is formed, whose cytoplasm is azurophilic. Megakaryocytes represent only one percent of the hematopoietic cells of the red bone marrow. A small number of megakaryocytes are also present in the circulating blood, but most of these are filtered out in the pulmonary capillaries.
Anatomy and structure
Megakaryocytes originally form from pluripotent stem cells. Pluripotent stem cells are embryonic cells of the bone marrow that can still differentiate into all body organs. These stem cells initially develop into megakaryoblasts, which can no longer divide by mitosis. However, continuous endomitosis takes place, which eventually leads to mature megakaryocytes. In endomitosis, only chromatids divide, but not the nuclei and cells. Thus, the cell enlarges more and more and forms polyploid chromosome sets. In this process, the 64-fold chromosome set can form. However, 128-fold chromosome sets have also been observed. Due to the enlargement of chromosome sets, megakaryocytes become the largest cells in the bone marrow. They can reach a diameter of 35 to 150 micrometers. By light microscopy, it looks as if there are multiple nuclei because the nucleus is irregularly lobed and contains coarse-grained chromatin. The cytoplasm of megakaryocytes is characterized by a large number of mitochondria and ribosomes, as well as a huge Golgi apparatus and a distinct endoplasmic reticulum. In addition, the same granules are present as in platelets. These are alpha granules, lysosomes, and electron-dense granules. These granules contain the active substances and proteins that stimulate platelet formation. Among them are growth and coagulation factors, calcium, ADP, and ATP.
Function and tasks
Megakaryocytes are the initial cells for platelet formation. Platelets are also known as blood platelets. When activated, they release substances to stop bleeding. After an injury, aggregation and adhesion of platelets takes place. In this process, the injured area is sealed by fibrin formation and bleeding stops. Platelets represent small cells without a nucleus. But RNA and various cell organelles are present and capable of biosynthesis of active substances for hemostasis. The whole process from the formation of platelets from pluripotent stem cells through megakaryoblasts and megakaryocytes is called thrombopoiesis. Initially, the myeloid stem cell (hemocytoplast) develops receptors for the hormone thrombopoietin. When these receptors have formed, the hemocytoplast becomes a megakaryoblast. The hormone thrombopoietin docks at the receptor and induces endomitosis, in which only division of the chromatin, but not of the nucleus and cell, occurs. The cell, which grows larger and larger, develops into a mature megakaryocyte under constant stalling of leaflets. During this process, four to eight proleaflets can be formed per cell. One proplatelet in turn gives rise to 1000 platelets. Therefore, between 4000 and 8000 platelets can develop from one megakaryocyte. The hormone thrombopoietin is taken up by megakaryoblasts and megakaryocytes via receptors and constantly forms platelets under endomitosis. Within the megakaryocytes and platelets, the hormone is degraded again.Thrombopoietin is formed in the liver, kidney and bone marrow. Since thrombopoietin degrades within megakaryocytes and platelets, a high concentration of thrombopoietin in the blood correlates with a low concentration of megakaryocytes and platelets. This stops the synthesis of the hormone. If the number of megakaryocytes and platelets increases, the synthesis of thrombopoietin is stimulated again by the decrease in its concentration in the blood.
Diseases
Disturbances in the regulatory mechanism can lead to uncontrolled platelet formation from megakaryocytes. This disorder is called essential thrombocythemia. In essential thrombocythemia, the concentration of platelets in the blood can reach 500,000 per microliter. The normal value is 150,000 to 350,000 per microliter. The cause is thought to be the increased sensitivity of megakaryocytes to the hormone thrombopoietin. Abnormally large, mature megakaryocytes are found in the bone marrow. The clinical picture is characterized by microcirculatory disturbances and functional complaints. There is an increased risk of stroke and myocardial infarction due to thromboembolism. Lack of blood flow to important regions of the body can lead to pain when walking, emptiness in the head or visual disturbances. Furthermore, upper abdominal pain may occur due to an enlarged liver or spleen. Decreased platelet production, in turn, is called thrombocytopenia. Its cause may be, among other reasons, an impaired formation of platelets in the bone marrow. Thrombocytopenia only becomes noticeable at a platelet concentration of 80,000 per microliter due to an increased bleeding tendency. Frequent hematomas, petechiae of the skin, nosebleeds, or cerebral hemorrhages are to be expected.
