Bleeding stops due to blood clotting. Clotting occurs when various proteins and other factors recreate fibers in the skin to stop the bleeding and restore the skin tissues broken or injured. Platelets, a component of our blood, are primarily responsible for blood clotting. However, to what should we be thankful for that we have platelets in our blood? Megakaryocytes.
What are Megakaryocytes (MKs) and what do they do?
Megakaryocytes produce platelets.
Platelets are tiny cell fragments that do not have nucleus. They are discoid in shape and are about one to three micrometer in diameter. They are responsible for processes such as equilibrium in the blood (hemostasis) and wound healing among other functions. As you will later on understand, platelets are formed from the cytoplasm of megakaryocytes (MKs), their precursor cells, which reside in the bone marrow.
Megakaryocytes are the largest cells in the bone marrow.
A megakaryocyte (MK) is a large bone marrow cell about 50 to 100 micrometer (a micrometer is expressed as μm; 1 micrometer is equal to 1×10−6 of a meter), which makes it 10 to 15 times larger than a typical red blood cell (RBC).
As it develops, the megakaryocyte grows in size. It replicates its DNA without ever dividing (this process is called endomitosis). Thus, it may contain multiple copies of a normal set of human DNA in a single cell. This explains why megakaryocytes become very large and lobulated.
Megakaryocytes are the most rare cells in the bone marrow.
For every ten thousand (10 000) bone marrow cell, you can only find one (1) megakaryocyte.
Megakaryocytes are progenitor cells.
A progenitor cell is a biological cell that differentiates into a specific type of cell depending on the signals it receives. Progenitor cells are unipotent cells, and are similar with stem cells to some extent. However, stem cells are multipotent, which means they can become different types of fully differentiated cells. Progenitor cells are unipotent cells; they can only become what they are dictated to become depending on the signals they receive.
Megakaryocytes are cancer fighters.
In 2010, the journal Blood reported an astounding finding of a team of scientists led by Dr. Alexander Zaslavsky. Dr. Zaslavsky and his colleagues observed that megakaryocytes (MKs) absorb circulating thrombospondin-1 (TSP-1) in tumor-bearing mice, and increase its synthesis to produce platelets with elevated levels of TSP-1. TSP-1 is a kind of protein that inhibits the production of tumor cells. The platelets with increased levels of TSP-1 adhere to tumors and act as inhibitors of tumor growth.
Moreover, they have noticed that MKs respond to the presence of tumors by increasing their number in the bone marrow to absorb as much TSP-1 and produce as much TSP-1 enriched platelets.
How are Megakaryocytes (MKs) formed?
MK Differentiation: Megakaryocytes are derived from another kind of cell in the bone marrow.
Megakaryocytes (MK) are progenitor cells that produce platelets. But what produces megakaryocytes? – A parent cell called hematopoietic stem cell (HSCs). HSCs are pluripotential stem cells located in the red bone marrow (“pluri” means “many”; “hema” means “blood”) that means that they give rise to all blood cells depending on the type of signals these HSCs receive. The primary signal for megakaryocyte production is called thrombopoietin or TPO, a kind of an amino acid protein mainly produced in the liver (but can also be made by the brain, testes, kidneys, and bone marrow stromal cells). So, TPO signals these pluripotential stem cells to start creating MKs.
MK maturation: Pluripotential hematopoietic stem cells (HSCs) become Megakaryoblasts.
After receiving the signal from the TPO to create MKs, hematopoietic stem cells embark on a process called endomitosis or the replication of DNA without making the cell to divide. Ergo, it becomes bigger and bigger as DNA accumulates, and then, a megakaryoblast is created – a baby megakaryocyte. It is about 8 to 30 micrometer big (compared to a 50 – 100 micrometer mature megakaryocyte). Then, as it gets bigger, it will be called a promegakaryocyte. It will now complete its maturation process and produce platelets.
MK’s terminal development and proplatelet and platelet production
Megakaryocytes (MKs) maturation process is characterized by massive nuclear proliferation and enlargement of the MK cytoplasm (the parts of the cell other than the nucleus; includes various organelles or ‘contents’) occur as the MK is filled with cytoskeletal proteins, platelet-specific granules, and sufficient membrane to complete the platelet assembly process.
After maturation, MKs extrude their nucleus and repackage the bulk of their cytoplasm into multiple long processes called proplatelets – a protrusion that elongates over time. Now, MKs generate preplatelets, which undergo subsequent fission events to generate discoid platelets.
This entire process takes place in approximately 5 days.
What happens when something goes wrong with Megakaryocytes?
Without megakaryocytes, it is impossible to produce platelets. Without platelets, it is impossible for humans to survive an injury. Abnormalities in megakaryocytes or in the production thereof, means serious consequence to human health.
Too many megakaryocytes lead to excessive clotting.
Under normal condition, there are approximately 150,000 to 400,000 platelets per microliter of human blood. But when platelets per microliter of blood exceeds 600 000, a condition called essential thrombocytosis or essential thrombocythemia occurs. It is characterized by clotting throughout the body. Clots may also form in arteries and veins (more frequently in arteries than in veins); the consequence could be hemorrhagic.
This happens when during endomitosis, the megakaryocyte becomes too sensitive to TPO (TPO commands MKs to replicate DNA and not divide) and then creates too much platelet. Or, when their precursor cells, HSCs, become too sensitive to TPO (TPO commands HSCs to create MKs) and create too many MKs (therefore too many platelets).
Too few megakaryocytes may lead to excessive bleeding.
When the platelet count per microliter of blood drops below 50 000, a condition called thrombocytopenia may occur. It is characterized by external bleeding such as nosebleed, gum bleeding, or prolonged menstruation (for women). Purpura or bruising may also be observed, and other forms of bleeding disorders or coagulopathy. While thrombocytopenia may not usually be physically observed, it can be diagnosed through routinely checking the blood count.
- READ MORE