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Stem cells and haemopoiesis 

Stem cells and haemopoiesis

Chapter:
Stem cells and haemopoiesis
Author(s):

C. A. Sieff

DOI:
10.1093/med/9780199204854.003.220201_update_001

Update:

Chapter reviewed. Updates made to sections on phylogeny and ontogeny, negative regulation of erythropoiesis, and clinical studies with haemopoietic growth factors.

Updated on 30 May 2013. The previous version of this content can be found here.
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date: 25 March 2017

Haemopoiesis is the process of the amplification and terminal differentiation of immature precursors of the formed elements of the blood. A complex but ordered process proceeds via stem cells, progenitor cells, and precursor cells to produce mature cells of many lineages—erythrocytes, platelets, basophils, polymorphonuclear leucocytes, monocyte/macrophages, eosinophils, and a variety of types of lymphocyte.

Mechanisms of haemopoiesis

Key elements—(1) Pluripotent stem cells—present at extremely low frequency in marrow (1 in 104–105 cells); capable of both self-renewal and multilineage differentiation under the influence of certain non-lineage-specific growth factors such as Flt-3 ligand, stem cell factor (SCF), interleukin 6, and thrombopoietin. (2) Committed progenitor progeny—present at frequency in marrow of 1 in 103 cells; the level in the process at which amplification of blood-cell production occurs; limited proliferative potential that depends upon the presence of specific growth factors. (3) An appropriate microenvironment for haemopoietic differentiation, which in normal adults is confined to the bone marrow.

Particular cell lineages—(1) Erythropoiesis—release of erythropoietin from specialized peritubular cells in the kidney by anaemia or hypoxia stimulates the division and differentiation of erythroid progenitors and erythroblasts. (2) Myelopoiesis—under the influence of unique colony-stimulating factors (CSF), granulocyte and monocyte progenitors differentiate into mature granulocytes and monocytes, the latter leaving the circulation and differentiating further to become fixed tissue macrophages. (3) Megakaryocytopoiesis—thrombopoietin induces lineage-restricted megakaryocyte progenitor proliferation and differentiation of megakaryoblasts to the megakaryocytes that in turn produce platelets.

Marrow anatomy—the melange of cells within the marrow exist in delicate fronds thrust into the venous sinuses. Cells are packed in close proximity within the fronds, held together by extensions of fibroblast cytoplasm and fibronectin. Such delicate anatomy is subject to many abnormalities that can disturb the orderly progress of cell–cell interactions that govern the system, with the multiple symptoms of bone marrow failure resulting from such disturbances.

Clinical use of haemopoietic growth factors

Several recombinant haemopoietic growth factors are in clinical use, including (1) erythropoietin—to treat the anaemia of advanced chronic kidney disease (and sometimes other anaemias); (2) G-CSF—to shorten the period of neutropenia following myelosuppressive anticancer chemotherapy, and for reduction of infection in severe congential neutropenia and in some patients with nonmyeloid malignancies; (3) GM-CSF—to accelerate haemopoietic reconstitution after bone marrow transplantation (also G-CSF).

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