MEGAKARYOCYTES: CHARACTERISTICS, STRUCTURE, FORMATION, MATURATION - BIOLOGY - 2025

The megakaryocytes are cells of considerable size, whose fragmentation cell gives rise to platelets. In the literature they are considered "giant" cells that exceed 50 um, which is why they are the largest cellular elements of hematopoietic tissue.

In the maturation of these cells, several particular stages stand out. For example, the acquisition of multiple nuclei (polyploidy) through consecutive cell divisions where DNA is multiplied but there is no cytokinesis. In addition to the increase in DNA, different types of granules also accumulate.

Source: Wbensmith

Most of these cells are located in the bone marrow, where they correspond to less than 1% of the total cells. Despite this low cell ratio, the fragmentation of a single mature megakaryocyte gives rise to many platelets, between 2,000 and 7,000 platelets, in a process that lasts about a week.

The passage from megakaryocyte to platelets occurs by strangulations in the membranes of the former, followed by the separation and release of newly formed platelets. A series of molecular elements - mainly thrombopoietin - is responsible for orchestrating the process.

The elements derived from these cells are platelets, also called thrombocytes. These are small cell fragments and lack a nucleus. Platelets are found as part of the blood and are essential in the process of blood clotting or hemostasis, wound healing, angiogenesis, inflammation and innate immunity.

Historical perspective

The process by which platelets originate has been studied for more than 100 years. In 1869 a biologist from Italy named Giulio Bizzozero described what appeared to be a giant cell, more than 45 um in diameter.

However, these peculiar cells (in terms of their size) were not related to the origin of platelets until 1906. Researcher James Homer Wright established that the giant cells initially described were the precursors of platelets, and named them megakaryocytes.

Subsequently, with advances in microscopy techniques, structural and functional aspects of these cells were elucidated, in which the contributions of Quick and Brinkhous to this field stand out.

Characteristics and structure

Megakaryocytes: Progenitors of Platelets

Megakaryocytes are cells that participate in the genesis of platelets. As its name indicates, the megakaryocyte is large, and is considered the largest cell within the hematopoietic processes. Its dimensions are between 50 and 150 um in diameter.

Nucleus and cytoplasm

In addition to its prominent size, one of the most conspicuous characteristics of this cell lineage is the presence of multiple nuclei. Thanks to the property, it is considered a polyploid cell, since it has more than two sets of chromosomes within these structures.

The production of the multiple nuclei occurs in the formation of the megakaryocyte from the megakaryoblast, where the nucleus can divide so many times that a megakaryocyte has from 8 to 64 nuclei, on average. These nuclei can be hypo or hyperlobulated. This occurs due to the phenomenon of endomitosis, which will be discussed later.

However, megakaryocytes presenting only one or two nuclei have also been reported.

As for the cytoplasm, it increases significantly in volume, followed by each division process and presents a large number of granules.

Location and quantity

The most important location for these cells is the bone marrow, although they can also be found to a lesser extent in the lungs and spleen. Under normal conditions, megakaryocytes make up less than 1% of all cells in the marrow.

Due to the considerable size of these progenitor cells, the body does not produce a large number of megakaryocytes, since a single cell will produce many platelets - unlike the production of the other cellular elements that need multiple progenitor cells.

In an average human being, up to 10 ⁸ megakaryocytes can form each day, giving rise to more than 10 ¹¹ platelets. This amount of platelets helps maintain a steady state of circulating platelets.

Recent studies have highlighted the importance of lung tissue as a platelet-forming region.

Features

Megakaryocytes are essential cells in the process called thrombopoiesis. The latter consists of the generation of platelets, which are cellular elements of 2 to 4 um, round or ovoid in shape, lacking nuclear structure and located inside the blood vessels as blood components.

Since they lack a nucleus, hematologists prefer to call them cell "fragments" and not cells as such - as are red and white blood cells.

These cell fragments play a crucial role in blood clotting, maintain the integrity of blood vessels, and participate in inflammatory processes.

When the body experiences some type of injury, platelets have the ability to quickly adhere to each other, where a protein secretion begins that initiates clot formation.

Formation and maturation

Formation scheme: from megakaryoblast to platelets

As we mentioned earlier, the megakaryocyte is one of the precursor cells for platelets. Like the genesis of other cellular elements, the formation of platelets - and therefore megakaryocytes - begins with a stem cell with pluripotent properties.

Megakaryoblast

The cellular precursors of the process start with a structure called megakaryoblast, which duplicates its nucleus but does not duplicate the entire cell (this process is known in the literature as endomitosis) to form the megakaryocyte.

Promegacariocito

The stage that occurs immediately after the megakaryoblast is called the promegakaryocyte, followed by the granular megakaryocyte and finally the platelet.

In the first stages, the nucleus of the cell has some lobes and the protoplasm is of the basophilic type. As the megakaryocyte stage approaches, the protoplasm progressively becomes eosinophilic.

Granular megakaryocyte

Megakaryocyte maturation is accompanied by a loss of the ability to proliferate.

As its name indicates, in the megakaryocyte of the granular type it is possible to distinguish certain granules that will be observed in the platelets.

Once the megakaryocyte matures it goes to the endothelial cell of the vascular sinusoid of the medulla and begins its path as a platelet megakaryocyte

Platelet megakaryocyte

The second type of megakaryocyte called platelet is characterized by the emission of digital processes that arise from the cell membrane called protoplasmic herniations. The granules mentioned above move to these regions.

As the cell matures, each herniation undergoes strangulation. The result of this disintegration process ends with the release of cell fragments, which are nothing more than platelets already formed. During this stage, most of the cytoplasm of the megakaryocyte is transformed into small platelets.

Regulatory factors

The different stages described, ranging from megakaryoblast to platelets, are regulated by a series of chemical molecules. The maturation of the megakaryocyte has to be delayed along its journey from the osteoblastic to the vascular niche.

During this journey, collagen fibers play a fundamental role in inhibiting the formation of protoplatelets. In contrast, the cellular matrix corresponding to the vascular niche is rich in von Willebrand factor and fibrinogen, which stimulate thrombopoiesis.

Other key regulatory factors of megakaryocytopoiesis are cytokines and growth factors such as thrombopoietin, interleukins, among others. Thrombopoietin is found as a very important regulator throughout the entire process, from proliferation to cell maturity.

Furthermore, when platelets die (programmed cell death) they express phosphatidylserine in the membrane to promote removal thanks to the monocyte-macrophage system. This cellular aging process is associated with the desialinization of glycoproteins in platelets.

The latter are recognized by receptors called Ashwell-Morell on liver cells. This represents an additional mechanism for the elimination of platelet debris.

This hepatic event induces the synthesis of thrombopoietin, to initiate the synthesis of platelets again, therefore it serves as a physiological regulator.

Endomitosis

The most remarkable - and curious - event in the maturation of megakaryoblasts is a process of cell division called endomitosis that gives the giant cell its polyploid character.

It consists of cycles of DNA replication uncoupled from cytokinesis or division of the cell per se. During the life cycle, the cell goes through a 2n proliferative state. In cell nomenclature n is used to designate a haploid, 2n corresponds to a diploid organism, and so on.

After the 2n state, the cell begins the endomitosis process and progressively begins to accumulate genetic material, namely: 4n, 8n, 16n, 64n, and so on. In some cells, genetic loads of up to 128n have been found.

Although the molecular mechanisms that orchestrate this division are not precisely known, an important role is attributed to a defect in cytokinesis as a result of malformations found in the proteins myosin II and actin F.

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