Blood-forming Stem Cells

Because of the short Ufespan of blood cells, it is unsurprising that bone marrow is a rich source of haematopoietic stem cells which form progenitors for erythrocytes, lymphocytes, granulocytes, platelets and monocytes. Interestingly, human mesenchymal... 

All mature blood cells arise from primitive hematopoietic cells in the bone marrow, the pluripotent stem cells. Approximately 0.1% of the nucleated cells of the bone marrow are pluripotent stem cells and approximately 5% of these cells may be actively cycling at any one time. The stem cell pool maintains itself through a process of asymmetrical cell division when a stem cell divides, one daughter cell remains a stem cell and the other becomes a committed colony-forming cell (CFC). The proliferation and differentiation of CFCs are controlled by hematopoietic growth factors. The hematopoietic growth factors stimulate cell division, differentiation and maturation, and convert the dividing cells into a population of terminally differentiated functional cells. 

Erythropoiesis is a process that starts with a pluripotent stem cell in the bone marrow that eventually differentiates into an erythroid colony-forming unit (CFU-E)4 (Fig. 63-1). The development of these cells depends on stimulation from the appropriate growth factors, primarily erythropoietin. Other cytokines involved include granulocyte-monocyte colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3). Eventually, the CFU-Es differentiate into reticulocytes and cross from the bone marrow into the peripheral blood. Finally, these reticulocytes mature into erythrocytes after 1 to 2 days in the bloodstream. Throughout this process, the cells gradually accumulate more hemoglobin and lose their nuclei.4... 

Hematopoiesis is defined as the development and maturation of blood cells and their precursors. In utero, hematopoiesis may occur in the liver, spleen, and bone marrow. However, after birth, it occurs exclusively in the bone marrow. All blood cells are generated from a common hematopoietic precursor, or stem cell. These stem cells are self-renewing and pluripotent and thus are able to commit to any one of the different lines of maturation that give rise to platelet-producing megakaryocytes, lymphoid, erythroid, and myeloid cells. The myeloid cell line produces monocytes, basophils, neutrophils, and eosinophils, whereas the lymphoid stem cell differentiates to form circulating B and T lymphocytes. In contrast to the ordered development of normal cells, the development of leukemia seems to represent an arrest in differentiation at an early phase in the continuum of stem cell to mature cell.1... 

FIGURE 2 9-3 Intravenous administration of stem cells can reconstitute the blood forming system, and may provide cells to other tissues. In classical studies, Till and McCulloch administered dissociated bone marrow cells in the tail vein of lethally irradiated mice and found that the grafted cells repopulated the hematopoietic system and allowed the animals to survive. More recent studies suggest that blood cells also travel to sites of injury, where they may give rise to non-blood-tissue progeny. 

The polymorph is the dominant white cell in the blood stream and, like the macrophage, shares a common hemopoietic stem cell precursor with the other formed elements of the blood. It has no mitochondria, but utilizes its abundant cytoplasmic glycogen stores for its energy requirements thus, glycolysis enables these cells to function under anaerobic conditions such as those in an inflammatory focus. It is a nondividing, short-lived cell with a segmented nucleus. 

In addition to erythrocytes, blood contains white blood cells, called leukocytes, of several types, and platelets, also called thrombocytes, which control blood clotting. Hematopoiesis (from the Greek, haimo, for blood, and poiein for to make ) is the process by which the elements of the blood are formed. The marrow of bone contains so-called stem cells which are immature predecessors of these three types of blood cells. Chemicals that are toxic to bone marrow can lead to anemia (decreased levels of erythrocytes), leukopenia (decreased numbers of leukocytes), or thrombocytopenia. Pancytopenia, a severe form of poisoning, refers to the reduction in circulatory levels of all three elements of the blood. One or more of these conditions can result from sufficiently intense exposure to chemicals such as benzene, arsenic, the explosive trinitrotoluene (TNT), gold, certain drugs, and ionizing radiation. Health consequences can range... 

Zambidis E, Oberlin E, Tavian M and Peault B (2006). Blood forming endothelium in human ontogeny lessons from in utero development and embryonic stem cell culture. Trends in Cardiovascular Medicine 16(3) 95 101. 

Figure 5.2 All types of blood cells are formed from uncommitted blood (hematopoietic) stem cells in a process called differentiation. Specific protein factors drive the development of erythrocytes (red blood cells), platelets, and the w/hite blood cells including neutrophils and eosinophils, basophils, all with multi-lobed nuclei, and the mononuclear monocytes and lymphocytes that provide specific protein and cellular defenses to the body.

Hematopoietic stem cells are used to treat people whose own blood-forming cells fail because of a rare condition called aplastic anemia, or to help people who have been accidentally exposed to very high doses of irradiation. Hematopoietic stem cells are most often used as part of the treatment for certain forms of cancer. Sometimes cancer patients are given very high doses of irradiation and/or chemotherapy drugs that destroy the blood-forming stem cells in the bone marrow. Transplants with the patient s own blood stem cells that were removed before the treatment, or stem cells from a healthy donor, allow the patient to recover. The transplant process is very simple The cells in a salt solution are slowly injected into a vein just like a blood transfusion. If the blood stem cells come from a donor, then the donor and the patient must share certain inherited proteins to make sure that the donor s immune system cells will not attack the treated patient. 

Nearly all the oxygen carried by whole blood in animals is bound and transported by hemoglobin in erythrocytes (red blood cells). Normal human erythrocytes are small (6 to 9 pm in diameter), biconcave disks. They are formed from precursor stem cells called hemocytoblasts. In... 

Every second of life a human must produce about 2.5 million red blood cells, about 2 million granulocytes, and many lymphocytes as well as other less numerous leukocytes. All of these arise from multipotential stem cells found in the bone marrow.376-379 Each of these stem cells divides to form one daughter stem cell and one progenitor cell.380 The progenitor cells are also stem cells but have differentiated into myeloid,381 erythroid, and lymphoid382 383 cells. 

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