Hematopoiesis stem cells

Figure 5.7. Hematopoiesis differentiation of HSCs to specialized cells. The differentiation from HSCs (hematopoiesis stem cells) is a complex process which is shown here. The relationships of the intermediate cells to each of the final mature forms are shown from top to bottom in this figure. The development is completed with the generation and specific spatial placement of the various specialized mature functional cell forms. [This image was obtained from HEAL (Health Education Assets Library) whose goal to provide free digital resources for health education (http //www.healcentral.org).] See insert for color representation of this figure.

Deficiency. Macrocytic anemia, megaloblastic anemia, and neurological symptoms characterize vitamin B 2 deficiency. Alterations in hematopoiesis occur because of the high requirement for vitamin B 2 for normal DNA repHcation necessary to sustain the rapid turnover of the erythrocytes. Abnormal DNA repHcation secondary to vitamin B 2 deficiency produces a defect in the nuclear maturational process of committed hematopoietic stem cells. As a result, the erythrocytes are either morphologically abnormal or die during development. 

Broudy VC (1997) Stem cell factor and hematopoiesis. Blood 90 1345-1364... 

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... 

In HSCT, very high doses of chemotherapy with or without total-body radiation (TBI) are given in an attempt to potentiate leukemia cell kill. Hematopoiesis is restored by the infusion of stem cells harvested from an HLA-compatible donor, thereby rescuing the patient from the consequences of total aplasia.13 It is the most effective antileukemic therapy currently available. 

Beyond roles of chemokine receptors in hematopoiesis and innate immunity, roles for chemokines in adaptive immunity emerged. Moreover, other nonleukocyte migration properties of chemokine receptors have been identified. These include roles in the biology of endothelial cells (Chapter 15), cancer (Chapter 16), smooth muscle (Chapter 11), fibroblasts (Chapter 14), stem cells (Chapter 8), and all cell types associated with nervous system tissues (Chapter 17). In many instances, broad functional overlap is evident as chemokines can direct the migration of these cells just as they do with leukocytes. In certain instances, the ability of chemokines to retain cell populations within a specific microenvironment is as important as their migration-promoting properties. However, it is also clear that migration and retention are not the sole end points. 

Key Words Stem cells chemokines hematopoiesis chemotaxis T cells B cells. 

Hu, X. and Zuckerman, K. 2001. Transforming growth factor signal transduction pathways, cell cycle mediation, and effects on hematopoiesis. Journal of Hematotherapy and Stem Cell Research 10(1), 67-74. 

The effects of Li+ upon hematopoiesis have been proposed to be due to two different systems modification of the activity of the membrane Na+/K+-ATPase, and the inhibition of adenylate cyclase. Monovalent cation flux, in particular Na+ transport, is known to influence the differentiation and proliferation of hematopoietic stem cells. For instance, ouabain, an effective inhibitor of the membrane Na+/K+-ATPase, blocks the proliferation of lymphocytes and has been shown to attenuate the Li+-induced proliferation of granulocyte precursors [208]. Conversely, Li+ can reverse the actions of amphotericin and monensin, which mediate Na+ transport and which inhibit CFU-GM, CFU-E, and CFU-MK colony formation in the absence of Li+ [209]. Therefore, the influence of Li+ upon normal physiological cation transport—for example, its influence upon Na+/K+-ATPase activity—may be partly responsible for the observed interference in hematopoiesis. 

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... 

In conclusion the present report confirms the significant impact of y-retroviral vector insertion sites on the establishment of clonal dominance in hematopoiesis after (serial) bone marrow transplantation. The identification of a number of putative sternness genes may contribute not only to a better understanding of stem cell biology but, in the long run also to the development of novel approaches for stem cell based therapeutic regimens, e.g. in regenerative medicine. 

SCF is encoded by the mouse Steel (SI) loci (Zsebo et al, 1990). The Sl-Dickie allele of mutant mice (Sf ) encodes a smaller protein due to deletions of the transmembrane and intracellular domains. SI cells exclusively express a secreted form of SCF (Flanagan et al, 1991). Another mutation of the Steel locus, Sl/Sl, results in complete loss of SCF production (Zsebo et al, 1990). Mutations of both the Steel and SI loci result in similar phenotypic disorders of hematopoiesis characterized by reduction in stem cell numbers, anemia, mast cell- and repair deficiencies (Nocka et al., 1989 McCulloch et al., 1965). Phenotypes of Sf mice show that the membrane inserted SCF must have an... 

An important stromal derived growth factor, SCF, appears to play a major role in mechanisms like this. SCF can be expressed as a membrane-bound molecule that can be subsequently cleaved to soluble protein. The physiological functions of these isoforms are not well known. The deficiencies in mature eythroid precursors and in pluripotent hematopoietic stem cells in SI mutant mice (McCulloch et al, 1965) indicated that the membrane-bound SCF isoform has an essential function in hematopoiesis. 

Abstract. G-CSF Is a major extracellular regulator of hematopoiesis and the most used cytokine in clinical practice. Coherently with and for a long time after the repeated injections of low doses of G-CSF the study of alterations in hematopoietic precursor cells concentration in the bone marrow of mice was undertaken. G-CSF treatment did not affect the number of granulocytes and oligopotent precursor cells (CFU-C). However, frequency of early multipotent stem cells (LTC-IC) decreased one month after the last (7 ) course of G-CSF injections, moreover it halved during the following year. The exhaustion of LTC-IC after G-CSF treatment is discussed. 

Drize N, Chertkov J, Samoilina N et al. Effect of c 4okine treatment (granuloc34e colony-stimulating factor and stem cell factor) on hematopoiesis and the circulating pool of hematopoietic stem cells in mice. Exp Hematol. 1996 24 816-822. 

HUMAN EMBRYONIC STEM CELLS CAN MODEL EMERGING ANGIO-HEMATOPOIESIS... 

Bmmmendorf TH, Balabanov S. Telomere length d3mamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover. Leukemia 2006 20 1706-1716. 

We currently established cultural system (amphycultural diffusion capsules) that allowed for conditions favorable for stem cell expansion in vitro. Many cell types and culture protocols and their combination with cytokines, growth factors, feeder layers can be implemented with ADC. Capsules are characterized by high perfusion rates that ensure that allow dilution of inhibitory autocrine factors and support long-term cell expansion. We have shown that ADC in vitro provides optimal cellular microenvironment that supports long term hematopoiesis (Bilko et al. 2005). 

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