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INTRODUCTION

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Mature blood cells have a relatively short life span and must be continuously replaced 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 that in the third trimester marrow of specific bones becomes the major hemopoietic organ.

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FIGURE 13–1

Shifting locations of hemopoiesis during development and aging.

Graphic Jump Location

Hemopoiesis, or blood cell formation, first occurs in a mesodermal cell population of the embryonic yolk sac, and shifts during the second trimester mainly to the developing liver, before becoming concentrated in newly formed bones during the last 2 months of gestation. Hemopoietic bone marrow occurs in many locations through puberty, but then becomes increasingly restricted to components of the axial skeleton.

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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 are pluripotent cells capable of asymmetric division and self-renewal. Some of their daughter cells form 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. Stem cells are studied using experimental techniques that permit analysis of hemopoiesis in vivo and in vitro.

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In vivo techniques include injecting the bone marrow of normal donor mice into irradiated mice whose hematopoietic cells have been destroyed. 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 are used to identify and study the cytokines promoting hemopoietic cell growth and differentiation.

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