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Mature blood cells have a relatively short life span and require continuous replacement with new cells from precursors developing during hemopoiesis (Gr. haima, blood + poiesis, a making). In the early embryo these blood cells arise in the yolk sac mesoderm. In the second trimester hemopoiesis (also called hematopoiesis) occurs primarily in the developing liver, with the spleen playing a minor role (Figure 13–1). Skeletal elements begin to ossify and bone marrow develops in their medullary cavities, so in the third-trimester marrow of specific bones becomes the major hemopoietic organ.
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Throughout childhood and adult life, erythrocytes, granulocytes, monocytes, and platelets continue to form from stem cells located in bone marrow. The origin and maturation of these cells are termed, respectively, erythropoiesis (Gr. erythros, red + poiesis), granulopoiesis, monocytopoiesis, and thrombocytopoiesis. As described in Chapter 14 on the immune system, lymphopoiesis or lymphocyte development occurs in the marrow and in the lymphoid organs to which precursor cells migrate from marrow.
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This chapter describes the stem and progenitor cells of hemopoiesis, the histology of bone marrow, the major stages of red and white blood cell differentiation, and platelet formation.
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STEM CELLS, GROWTH FACTORS, & DIFFERENTIATION
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As discussed in Chapter 3, stem cells represent pluripotent cells capable of asymmetric division and self-renewal. Some of their daughter cells develop as specific, irreversibly committed progenitor cells, and other daughter cells remain as a small pool of slowly dividing stem cells.
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Hemopoietic stem cells can be isolated by using fluorescence-labeled antibodies to mark specific cell surface antigens and passing the cell population through a fluorescence-activated cell-sorting (FACS) instrument. Research on hemopoietic stem cells utilizes experimental techniques permitting analysis in vivo and in vitro.
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In vivo techniques include injecting the bone marrow of normal donor mice with their own hematopoietic cells destroyed by radiation. In these animals only, the transplanted bone marrow cells produce hematopoietic colonies in the bone marrow and spleen, simplifying studies of this process. This work led to the clinical use of bone marrow transplants to treat potentially lethal hemopoietic disorders.
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In vitro techniques using semisolid tissue culture media containing substances produced by marrow stromal cells allow identification and study of cytokines promoting hemopoietic cell growth and differentiation.