Hematopoiesis regulation

Hematopoiesis Regulation Regulation of the behavior of early hematopoietic progenitor cells (HPCs) can be analyzed by MSC-HPC cocultures in vitro [54]. 

Hematopoietic (blood) cells transport oxygen and carbon dioxide, contribute to host immunity, and facilitate blood clotting [1], A complex, interrelated, and multistep process, called hematopoiesis, controls the production as well as the development of specific marrow cells from immature precursor cells to functional mature blood cells. This well-regulated process also allows for replacement of cells lost through daily physiologic activities. The proliferation of precursor cells, the maturation of these into mature cells, and the survival of hematopoietic cells require the presence of specific growth factors. 

Broxmeyer HE, Kim CH. Regulation of hematopoiesis in a sea of chemokine family members with a plethora of redundant activities. Exp Hematol 1999 27(7) 1113—1123. 

Katz, H. J. (1970). Transferrin and its function in the regulation of iron metabolism, page 539 in Regulation of Hematopoiesis, Vol. 1, Gordon, A. D., Ed. (Appleton-Century-Crofts, New York). 

As with the development of other organ systems, the development of the immune system is a highly regulated process. Table 19.1 and Figure 19.1 provide a list of known events or markers that occur during immune system development. In humans, hematopoiesis begins at approximately 3-4 weeks of gestation with the development of blood... 

Cytokines are produced mainly by the leukocytes (white blood cells). They are potent polypeptide molecules that regulate the immune and inflammation functions, as well as hematopoiesis (production of blood cells) and wound healing. There are two major classes of cytokines (1) lymphokines and monokines and (2) growth factors. 

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. 

Iversen PO, Woldbaek PR, Tonnessen T, et al. Decreased hematopoiesis in bone marrow of mice with congestive heart failure. Am J Physiol Regul Tntegr Comp Physiol. Jan 2002 282(1) R166-172. 

The last potential mechanism to be discussed in this chapter is drug-induced altered receptor expression. Hematopoiesis is a very intricate process that is regulated by cytokines and cell-cell interactions. Interruption with any of these processes can result in hematotoxicity. For example, zidovudine (AZT) decreases Epo [27], GM-CSFaand to lesser extent IL-3 receptor expression [7]. Decrease in the expression of the above receptors seems to lead to anemia and neutropenia, by decreasing the number of CFU-E and CFU-GM, respectively. 

As outhned earUer every single step of hematopoiesis is regulated and controlled in vivo by the cell s microenvironment. This not only includes the composition and concentration of growth factors, but also the local oxygen concentration, the pH, the osmolaHty, the supply of nutrients and the cellular and molecular surrounding of the cells (cell-cell contact, adhesion molecules and extracellular matrix). All these parameters affect the fate of the cell and, to estabUsh a cell culture process to cultivate or generate a specific subpopulation, the influence of all these factors has to be considered in the experimental set-up. In the following sections these parameters will be discussed in brief. 

The regulation of hematopoiesis in the bone marrow is not only controlled by the cytokine composition, the cells microenvironment and the oxygen tension, but, as shown recently [55], also by the local pH. For cells of different Hneages deviating pH optima have been described. While CFU-GM proliferate best in a pH range 7.2 - 7.4 (the normal pH of blood), for erythroid cells an optimum of pH 7.6 was found. Below an acidic pH of 6.7 no differentiation or proUferation of any hematopoietic cell was observed. Cells of the erythroid lineage are even strongly inhibited at a pH below 7.1 [56]. 

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