Stem Cells in the Blood
By M. William Lensch, Ph.D.
The blood-producing, or hematopoietic, stem cells are a type of “adult” stem cell. They are the best understood of all stem cells, because they are relatively simple to obtain from the blood itself, or from the bone marrow. The bone marrow is the blood-forming tissue and is the home of the blood stem cell; the predominant place where this cell divides and generates all the types of cells that make up the blood.
Access to the blood and bone marrow has allowed hematopoietic cell biology to be studied for a very long time. The earliest scientific works describing blood stem cells are nearly 100 years old (such as (Maximow, 1909) and (Danchakoff, 1916) ). Though these early scientists could not purify stem cells, they studied blood under the microscope and described it in great detail.
Even in these early days, some scientists suspected that a cell existed in our body that was capable of making the many types of cells found in the blood that are required for health. They could see that these cells become damaged or lost due to disease or other injury and that replacing them would be of considerable medical benefit. It was nearly 50 years ago that Dr. E. Donnall Thomas first published an attempt to transplant blood-forming tissue (bone marrow) from one person to another (Thomas et al., 1957) . This was the first bone marrow transplant, a treatment now known to work because blood stem cells are contained within the transplanted marrow.
Figure 1.
(Click for enlarged view) 
The formation of blood is a hierarchy of development starting with the hematopoietic stem cell (HSC). As the HSC divides, many different types of cells form. Just beyond the HSC, there is a cell that is known as a “hematopoietic progenitor cell” or HPC. Progenitors are not quite the same as stem cells though they share important characteristics. While progenitor cells have an incredible capacity to divide and make other types of cells as they mature, they have only a limited ability to self-renew. The HPC divides and forms more specialized blood cell types that in turn form even more specialized cell types. Ultimately, this generates an array of cells with different functions; our lymphoid blood cells (the B-cells; T-cells; natural killer or NK cells; plasma cells; dendritic cells and others) and our erythroid and myeloid blood cells (the erythrocytes or red blood cells; megakaryocytes or platelet producing cells; granulocytes such as neutrophils, eosinophils, and basophils; and monocytes which make macrophages).
|
|
Today, we are able to purify highly-enriched populations of blood stem cells from the bone marrow, peripheral blood, and also cord blood. The percentage of these stem cells present in the blood is highest during development in the uterus.
When humans are born, the blood still contains many blood stem cells and this is why umbilical cord blood has been used as an important source of blood-producing stem cells in recent years (for a very detailed review, please see Lensch and Daley, 2004).
All of these sources of blood stem cells continue to have important medical uses to restore a patient’s blood tissue following radiation or chemical exposures (such as during chemo- and radiation therapy) or to treat various blood diseases, including immunodeficiency.
Having access to purified populations of blood stem cells has also allowed the development of precise approaches to understanding how they form, how they are maintained in our bodies (and where), and how they might be used to better treat disease. So, what exactly is blood?
When functioning normally, an adult person’s circulating blood system contains about one hundred billion cells at any given time (that’s 100,000,000,000). The blood is made up of a number of different cell types, each with a specialized function such as carrying oxygen or repairing damaged blood vessels or immunity to infections. |
The majority of the cells in the circulating blood (99.9% or 999 in every 1,000) are the oxygen-carrying red blood cells known as erythrocytes. Red blood cells have a unique feature among human cells in that they lose their DNA-containing nucleus just prior to becoming fully mature, and are thus called anucleate. Also, it is erythrocytes that make our blood red due to the chemistry associated with their hemoglobin iron content.
The remaining 0.1% of total blood cells keep their nucleus. These are the white blood cells, or leukocytes. Of this fraction, many are a type of cell called a neutrophil (about 0.06% of the blood), with lymphocytes (cells of the immune system) next at 0.03%, and all other types falling within the remaining 0.01%. Some of these cells, such as certain T-cells, can live for decades in our bodies.
Indeed, the longevity of these T-cells is why we maintain immune system “memory” to childhood diseases even when we are old and grey. However, most blood cells do not last very long in our bodies before they need to be replaced due to ageing or damage, and this includes the erythrocytes that are turned over very rapidly in our bodies, lasting only 100 to 120 days before they are recycled.
In all, the demands placed upon our blood system are such that it replaces worn and damaged cells at a rate of literally billions per day. The systems that regulate this replacement process are both intricate and beautiful (at least to a hematology researcher such as me). The multitudes of blood cells circulating in your body at this very moment started their existence from a single cell in your bone marrow, the blood stem cell or hematopoietic stem cell (HSC).
The HSC is a rare cell that typically makes up less than 1/100 of a percent (0.01%) of the nucleated cells in the bone marrow. Although this is such a low percentage, there are so many blood cells in total that each person has many blood stem cells. These HSCs are not all active at once. Most of them lie dormant waiting for their turn to cycle into blood production.
The HSC is the most primitive cell in our blood system and it is from this cell that all other blood cells are derived as the HSC “differentiates” or matures to have a specialized function. The HSC must also do one other important thing, something shared by all cells known as “stem cells”, and that is to “self-renew”. Self-renewal simply means that the stem cell makes more copies of itself.
If the HSC did not self-renew (and only divided to make mature, specialized cells) our stem cell pool would eventually be exhausted and our blood-forming ability would run out. Because of these two properties, the HSC (and only the HSC) has the capacity to restore all blood formation for life in a transplanted person (or laboratory animal such as a mouse) that has lost their own hematopoietic tissue.
If we look at the chain of events leading to the formation of specialized blood cells that carry out defined functions (such as carrying oxygen or repairing damaged blood vessels), we see a hierarchy of development starting with the HSC (see Figure 1). Just beyond the HSC, there is a cell that is known as a “hematopoietic progenitor cell” or HPC. The HPC divides and forms more specialized blood cell types, and these in turn divide and form even more specialized cell types. Ultimately, this generates an array of blood cells with different functions.
Each different cell type has its own special characteristics and looks different under a microscope. It has been said that a trained hematologist may be able to recognize perhaps 150 different blood cell types among the normal blood cells, their progenitors, and other rare cells seen in certain diseases (did you know that some people have “buffalo cells” or “Howell-Jolly bodies”; two types of red blood cell abnormalities?).
The study of the blood has taught us volumes about the intricacies of blood formation as it occurs in health as well as sickness. Along the way we have been the fortunate benefactors of this research as new and improved medical treatments have resulted from the countless hours of investigation.
This valuable information has extended its reach far beyond the blood system and serves as the foundation for our knowledge of all stem cells. While each type of stem cell will bear its own unique features, whether neural, mesenchymal or whatever, the common aspects of all stem cells- self-renewal and multi-lineage differentiation- were lessons first learned from the blood.
References
Danchakoff, V. (1916). Origin of blood cells. Development of the haematopoietic organs and regeneration of the blood cells from the standpoint of the monophyletic school. Anat Rec 10, 397-414.
Lensch, M. W., and Daley, G. Q. (2004). Origins of mammalian hematopoiesis: in vivo paradigms and in vitro models. Curr Top Dev Biol 60, 127-196.
Maximow, A. A. (1909). Der Lymphozyt als gemeinsame Stammzelle der verschiedenen Blutelemente in der embryonalen Entwicklung und im postfetalen Leben der Säugetiere. Folia Haematol 8, 125-134.
Thomas, E. D., Lochte, H. L., Jr., Lu, W. C., and Ferrebee, J. W. (1957). Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med 257, 491-496.
M. William Lensch, Ph.D., is affiliated with Children's Hospital Boston,
Harvard Medical School and Harvard Stem Cell Institute.
Back to Selected Topics
Updated:
March 20, 2006
|
