Haematopoiesis

Hematopoiesis (also spelled haematopoiesis) is the process by which blood cells are made in the body. This process ensures a person has a steady level of red blood cells, white blood cells, and platelets. The process occurs in the bone marrow of children and adults. It takes place in different parts of a fetus’s body. Stem cells inside the bone marrow change to become different types of blood cells. Diseases and disorders that affect hematopoiesis can be very dangerous, and sometimes, bone marrow transplantation is used to treat people with such diseases.

Background

Blood plays a vital role in the human body. It carries nutrients, such as oxygen and food, to different parts of the body. It also helps remove waste material, such as carbon dioxide, and chemicals leftover from processing food. Blood also helps protect the body from invading microorganisms, and it coagulates and helps the body protect itself when the skin is cut or punctured. Blood is made up of red blood cells (RBCs), white blood cells (WBCs), platelets, and plasma. RBCs carry oxygen in the blood. WBCs help fight off microorganisms. Platelets help the blood coagulate so wounds can heal. Plasma is a yellowish liquid that helps carry nutrients and hormones to different parts of the body. Plasma is made up of water, which comes from the fluids a person drinks, and specific proteins supplied by the liver. RBCs, WBCs, and platelets are all cells that the body needs to make. The process of making these three types of cells is called hematopoiesis.

Overview

Hematopoiesis takes place most often in the bone marrow. Bone marrow is the tissue inside axial and long bones. It has a sponge-like consistency. Blood vessels bring nutrients to the bone marrow, which has an extensive blood supply. Bone marrow also has nerves running through it. Most bone marrow are made up of hematopoietic tissue, including blood cells, stem cells, barrier cells, and adipocytes (fat cells).

The most important cells for hematopoiesis are the multipotent stem cells in the marrow. Multipotent stem cells are regenerated by the body and can develop into many different types of cells later. These cells, which are sometimes called master cells, are important because they can develop into many different types of blood cells to support oxygen transport, immunity, and clotting. They even help produce more stem cells. Hematopoiesis specifically involves multipotent hematopoietic stem cells (HSCs).

The first step in the process of hematopoiesis is for the multipotent stem cells to change into one type of precursor cell. These are not mature blood cells, but they have transformed enough so they are no longer stem cells. Precursor cells change into different forms, each becoming more like a mature blood cell. Eventually, the cells transform into the mature version of each type of blood cell.

During hematopoiesis, three types of cells are made: RBCs (also called erythrocytes), WBCs (also called leukocytes), and platelets (also called thrombocytes). Hematopoiesis involves the production of all three types, but each type also has a specific process that takes place in the marrow. Erythropoiesis is the process of making exclusively erythrocytes. This process takes place in specific areas in the bone. These erythroblastic islands are specific anatomical units in the marrow. In this part of the marrow, the multipotent stem cells change to unipotent stem cells, to proerythroblasts, to basophilic erythroblasts, to polychromatophilic erythroblasts, to orthochromatophilic erythroblasts, to reticulocytes, and to mature erythrocytes (or RBCs). Megakaryopoiesis is the process of making exclusively thrombocytes. During this process, the stem cells transform into megakaryocytes, which are very large cells with multilobed nuclei. These cells fragment and turn into platelets. Different types of white blood cells are made in different processes, but each process involves the multipotent stem cells transforming into precursor cells and the precursor cells eventually transforming into mature WBCs. Once RBCs and WBCs are formed, they enter the bloodstream through the wall of the venous sinuses. Platelets are released from the cytoplasm where they form in the bone marrow and enter the bloodstream.

Hematopoiesis most often happens in the bone marrow, but the location of the process changes while a fetus develops and throughout childhood into adulthood. In embryos, hematopoiesis begins in the yolk sac and then the liver. In fetuses, the location of the process also changes, although the liver still is involved in hematopoiesis until the fifth month, after which it slowly slows down. Between the third and seventh months of development, hematopoiesis occurs in the fetus’s spleen. Between the fourth and seventh months of development, the process also begins to occur in the fetus’s marrow cavity. At birth, hematopoiesis occurs mostly in a baby’s bone marrow, but it can occur in the spleen and liver if it is needed. Hematopoiesis occurs in the bone marrow of infants and children, but the number of sites in the marrow where it can occur decreases with age. The process occurs in the marrow of the upper end of the femur and humerus, skull, vertebrae, sternum, ribs, and pelvis of adults.

Hematopoietic stem cell transplantation (HSCT) is a medical procedure that helps patients with certain types of medical conditions, such as cancer, genetic diseases, and immune disorders. Diseases that affect hematopoiesis can be extremely dangerous, and HSCT can help treat these diseases. During this transplantation, healthy blood-forming stem cells collected from the bone marrow (or peripheral blood or umbilical cord blood) are transplanted into patients with certain conditions that affect the body’s ability to complete hematopoiesis. The procedure gives the patient an infusion of hematopoietic stem cells (hematopoietic progenitor cells). Before the transplantation can take place, the patient is treated with certain medications to make space in the marrow, to treat cancer cells, and to suppress the patient’s immune system so it does not reject the new cells. The healthy bone marrow can come from a patient’s own body or a donor. However, because of the demand for bone marrow and a lack of donors, medical professionals use bone marrow or stem cells from living donors, umbilical cord blood, or the patient’s own body, while using deceased organ donors as a source is being studied. Other scientists are developing lab-grown blood stem cells to support treatments for individuals with rare blood diseases.

Further HSCT research focused on reducing treatment-related toxicity and relapse rates by improving conditioning regimens and better managing graft-versus-host disease (GVHD). Advances in hematopoiesis research have improved patient outcomes and expanded treatment options. The approval from the US Food and Drug Administration (FDA) for Casgevy (exagamglogene autotemcel), a clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing therapy, marking a major milestone in treatments for conditions like sickle cell disease and transfusion-dependent beta thalassemia. These methods work by modifying a patient’s own stem cells to produce functional hemoglobin.

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