Regulation of Haematopoiesis

All blood cells arise from the haemaopoietic stem cell. The path along which the stem cell progeny matures is dictated by the needs of the body. Examples of this include production of neutrophilic leucocytes in acute infection, eosinophils in parasitic infections, erythrocytes in case of blood loss and platelets in case of thrombocytopenia.

Blood cell production is controlled by growth factors. There are two categories of growth factors.

  1. Factors affecting multi-lineage cells
  2. Factors affecting one lineage of cells

Two points about haemaopoietic growth factors need to be highlighted. Firstly, the categorisation described above is not water-tight. Some factors stimulate the growth both of multi-lineage cells and lineage committed cells. Granulocyte colony stimulating (G-CSF) factor and thrombopoietin (TPO) are examples of such factors. Secondly, the deficiency of some of the factors can be overcome by alternate pathways. This is known as redundancy.

Factors affecting multi-lineage cells

Factors that stimulate the growth of haemopoitic stem cells and committed progenitor cells Kit ligand, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, CSF1, IL-3, IL-4, IL-6, IL-11, IL-12, flt-3 ligand (FL), leukaemia inhibitory factor and thrombopoietin

Factors affecting one lineage of cells

Factors that stimulate the development of one lineage include

  1. G-CSF for neutrophils
  2. IL-5 for eosinophils
  3. IL-3 for basophils
  4. CSF-1 and GM-CSF for macrophages and monocytes
  5. IL-7 for lymphocytes
  6. Erythropoietin for erythrocytes
  7. Thrombopoietin for megakaryocytes and platelets

 

The Bone Marrow Microenvironment

Haemotopoiesis takes place in the bone marrow. The non-haemopoietic cells and their stroma forms what is known as the bone marrow microenvironment. The bone marrow microenvironment supports the growth of cells by secreting cytokines. The non-haemopoietic cells include mesenchymal stem cells, pericytes, osteocytes, adipocites, endothelial cells and nerve cells. The matrix is composed of fibrous proteins glycoproteins and proteoglycans. The microenvironment plays an important role in controlling haemapoiesis. It also appears to have a role in haematological malignancies.

Therapeutic Use of Haemopoietic Growth Factors

Stimulation of growth factor receptors has been used increase blood counts.

  1. Erythropoietin receptor: Recombinant (erythropoietin alpha, erythropoietin beta) and recombinant modified (darbepoietin alpha) erythropoietins are used for treatment of anaemia of chronic kidney disease and cancer chemotherapy.
  2. G-CSF receptor: Filgrastim and lenograstim are agonist of the G-CSF receptor. Pegfilgrastim is a pegylated form o filgrastim and has a longer half life.
  3. Thrombopoietin receptor: The two agonists of TPO receptor are eltrombopeg and romipolstim. Recombinant TPO carries the risk of thrombocytopenia due to autoantibodies and in not used. Romipolstin is a peptide TPO mimic and eltrombopeg is a small molecule agonist.

 

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