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Blood Adult Stem Cell: Stem and Progenitor Cells in Adults

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Blood Adult Stem Cell: Stem and Progenitor Cells in Adults

Adult stem cells are defined as undifferentiated, self-renewing cells that can further differentiate into needed cell types. Maintenance and restoration of tissue types necessitates these stem cells, especially in adult organisms that accrue tissue damage over time. Among the major adult stem cell types are hematopoietic, mesenchymal, and endothelial cells. These cell types occupy a major portion of adult stem cell research, as the actual origins of these cells are not yet fully understood. Even so, exploitation of adult stem cell technology has already led to years of successful bone marrow (adult hematopoietic stem cells) transplant, and paved the way for clinical testing of stem cell therapy. Controlled differentiation of these adult stem cells may hold the key for advanced stem cell transplantation.

Multi-Potential Hematopoietic Stem Cells

Hematopoietic Stem Cells (HSCs) are highly undifferentiated, and can become any kind of blood cell. They are thus defined as multi-potent stem cells. Due to the high demand for both red and white blood cells, HSCs must frequently undergo self-renewal and differentiation. Self-renewal occurs at a pace such that the HSC pool maintains a constant approximate size. Differentiation removes cells from the HSC pool and creates other cell types in variable quantities.

HSCs can immediately undergo two differentiated fates, into the common myeloid progenitor cells, or the common lymphoid progenitor cell. Erythrocytes (RBCs) and thrombocytes (platelets) are among the differentiated myeloid cell types. B and T lymphocytes are among the further differentiated lymphoid cell types. Many factors influence the fate of a differentiating HSC, including hormone and protein signaling. HSCs may also choose to undergo apoptosis or programmed cell death in the event that their presence is unneeded or harmful. The actual signaling system that causes apoptosis in these cells remains a mystery. It was found, however, that the protein BCL-2 promotes life in HSCs and thus helps prevent apoptosis. Lastly, HSCs may leave bone marrow and enter the bloodstream, now able to travel across the body. It is noted, however, that many of the cells that leave the marrow eventually return, for reasons that are still unknown. Research has shown that many of these migrating cells are non-dividing, or at least have limited self-renewing potential.

In human adults, a comparatively high concentration of HSCs is found in the bone marrow, especially in the epiphysis (ends) of long bones. Current hematopoietic stem cell transplantation typically utilizes the pelvic bone as the source of bone marrow. It is also known that HSCs can be found in circulating blood, though in a much smaller quantity. As it offers a less invasive procedure, research is being done seeking to use peripheral blood as a source of HSCs for transplantation. With less significance to adults, it is known that HSCs are found abundantly in umbilical cord blood. A growing field of research seeks to find uses for umbilical cord-extracted HSCs in adults.

While a defining characteristic of HSCs is self-renewal, these cells seem to be more able to divide earlier in life. Research has linked progressive telomere shortening with reduced self-renewal capacity. Thus, aged HSCs have a lower ability to self-renew and commonly adopt other fates (apoptosis, differentiation, migration). This is coupled with the fact that self-renewal in adults is a slow process to begin with. The presence of HSCs as found in mouse bone marrow is approximately 1 in 10,000 blood cells. This poses a significant challenge to researchers seeking to work with large quantities of cells.

Progenitor Cells

A progenitor cell is similar to a stem cell in that it has a variety of fates it can adopt, thus also making it multi-potent. It differs, however, in that it can self-renew only a selected number of times. By contrast, a HSC can theoretically divide indefinitely. Also unlike HSCs, progenitor cells are biased to further differentiate into target cells, rather than maintain growth or divide. In this regard, a progenitor cell is more like an undifferentiated intermediate cell type between HSCs and target cells

The common myeloid progenitor cell is still undifferentiate, and may adopt a wide variety of cell types. These progenitor cells have the capacity to become megakaryocytes, erythrocytes, mast cells, and myeloblasts. Megakaryocytes eventually form thrombocytes, while myeloblasts can form basophils, neutrophils, eosinophils, monocytes, and macrophages. Many of these pathways have intermediate cell types, some of which are also capable of self-renewal. Myeloid cells are especially important in that their products supply oxygen to the body (erythrocytes), are integral in the blood clotting cascade (thrombocytes), and form a critical response for the immune system (neutrophils, etc.). These functions continue until death and thus make myeloid progenitor cells critical for normal adult function.

Bone marrow examination of cells with Wright’s stain showing neutrophil precursors. Promyelocytes are shown in the middle, two metamyelocytes are next to it, and two band cells and segmented neutrophils are at top left. Progenitor cells have the capacity to become megakaryocytes, erythrocytes, mast cells, and myeloblasts. (Wikimedia Commons)

The second common class of progenitors is the lymphoid progenitor cell type. These cells give way to all lymphocytes, along with Natural Killer (NK) cells. B lymphocytes mature in the bone marrow, whereas T lymphocytes mature in the thymus. B cells can also further differentiate into antibody secreting plasma cells. NK cells are cytotoxic lymphocytes that can recognize infected cells without the assistance of antibodies. Lymphoid progenitor cells thus play a critical role in the adaptive immune system, the system that keeps memory of foreign pathogens.

Target Cells and Inducible Fates

It is over-simplistic and incorrect to say that each HSC can form one final differentiated cell. Cell divisions occur in various cell-type intermediates, influencing the final number of target cells. For example, a starting multi-potential HSC, if choosing the erythrocyte pathway, first differentiates into a myeloid progenitor and then a proerythroblast.

The proerythroblast differentiates into an erythroblast, and the pathway continues to normoblast, reticulocyte, and finally erythrocyte. Each of these intermediate cell types also divides at least once, creating many erythrocytes from one proerythroblast. These mitotic divisions are necessary to meet the high demand of specific blood cell types. Through a modified endomitotic mechanism, one megakaryocyte produces thousands of platelets. Modifications and divisions become very necessary to produce enough of the needed target cell.

Differentiation is not a random process. Instead, signaling molecules and proteins induce cells to differentiate into a particular type, normally based on need. Erythropoietin (sometimes called Hematopoietin) induces red blood cell formation by preventing proerythroblasts from entering the apoptosis pathway. Erythropoietin is both sufficient and necessary for promoting this fate. Similarly, Thrombopoietin induces the megakaryocyte differentiation pathway to yield thrombocytes. The factors alter the fate of HSCs and produce target cells according to need. For example, Thrombopoietin is more highly produced when platelets are in low supply or when more are needed for a blood clotting response.

Future Research and Therapeutic Application

The value of adult stem cell research, and more specifically HSC research, cannot be overstated. HSCs hold significant value in particular, as they can become any kind of blood cell type. The use of artificial factors to promote a particular fate may offer targeted approaches to tissue regeneration. Inducing differentiation into lymphocytes could prove to be therapeutic in those who are immunocompromised.

Inducing differentiation into erythrocytes could prove to be therapeutic in those who have a reduced oxygen carrying capacity. Harvesting stem cells for transplantation is not a new phenomenon, and thousands of lives have been saved as a result of bone marrow transplants. Less invasive methods of extraction, such as use of HSCs circulating in the blood, could improve transplant outcome and quicken recovery time. Artificial hematopoiesis could create blood that would solve the problem of shortages in blood banks. Future work could investigate the potential for HSCs to become cells of other tissue types, as current research has already shown that they can become hepatocytes. The broad versatility of HSCs has and will continue to bring them to the forefront in modern stem cell research.

Krishna S. Vyas

Sibi Rajendran

University of Kentucky College of Medicine

See Also: Blood Adult Stem Cell: Current Research on Isolation or Production of Therapeutic Cells; Blood Adult Stem Cell: Development and Regeneration Potential.

Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 167

Blood Adult Stem Cell: Stem and Progenitor Cells in Adults

Multi-Potential Hematopoietic Stem Cells

Progenitor Cells

Target Cells and Inducible Fates

Future Research and Therapeutic Application

Further Readings