NORMAL HAEMATOPOIESIS:
“The physiologic process of formation of blood cells is known as haematopoiesis.”
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| Figure.01. HAEMATOPOIESIS |
It proceeds through different stages starting from early embryonic life—mesoblastic stage (yolk sac), hepatic stage, and myeloid (bone marrow) stage. During embryonic and early fetal life, haematopoiesis occurs in the yolk sac (only erythroblasts) and the liver (all blood cells). Blood cell precursors first appear in yolk sac during third week of embryonic development. Definitive haematopoiesis, however, first begins in the mesoderm of intraembryonic aorta/gonad/mesonephros (AGM) region after several weeks. Some blood cell formation also occurs in the spleen (all blood cells), lymph nodes and thymus (mostly lymphocytes). Bone marrow starts producing blood cells around 3rd to 4th month and by birth becomes the exclusive site of blood cell formation.
Hierarchy of Haematopoiesis
All blood cells are derived from pleuripotent haematopoietic stem cells, which are present in small numbers in the bone marrow. The haematopoietic stem cell is the most primitive cell in the bone marrow. It has the ability of proliferation, self-renewal, and differentiation along several lineages.
The myeloid and lymphoid stem cells originate from the pleuripotent haematopoietic stem cell. From myeloid and lymphoid stem cells progressively
more committed progenitors, generating different types of blood cells. Ultimately progenitor cells committed to produce only a single type of cell are derived.
Haematopoietic Growth Factors (HGFs)
HGFs are a group of proteins that
1. regulate proliferation, differentiation, and maturation of haematopoietic progenitor cells,
2. influence the commitment of progenitors to specific lineages,
3. Affect the function and survival of mature blood cells. HGFs are produced by different types of cells, which include T lymphocytes, macrophages, fibroblasts, endothelial cells, and renal interstitial cells
Many of the HGFs have been produced by the recombinant DNA technology. Recently, recombinant GM-CSF, G-CSF and erythropoietin have been approved for clinical use in certain conditions in USA.
01) GM-CSF
1. GM-CSF stimulates proliferation, differentiation, and maturation of lineages committed to neutrophil and monocyte/macrophage.
2. Recombinant GM-CSF is used to enhance the myeloid recovery following autologous bone marrow transplantation in non-myeloid malignancies. It is also being used to increase stem cell harvest from peripheral blood in peripheral blood stem cell transplantation.
02) G-CSF
1. G-CSF stimulates myeloid progenitor cells (CFU-G) to form mature neutrophils.
2. Recombinant G-CSF is used to reduce duration and severity of neutropaenia in non-myeloid malignancies.
03) Erythropoietin
1. Erythropoietin is a glycoprotein produced in the kidneys (90%) and in the liver (10%). It
stimulates progenitor cells committed to erythroid lineage (CFU-E and BFU-E) to proliferate and differentiate.
2. It is indicated in patients with anaemia of chronic renal failure who are on dialysis.
The Haematopoietic Microenvironment
The existence of haematopoietic microenvironment is suggested by the fact that formation of blood cells is restricted specifically to bone marrow. The exact nature of the microenvironment is poorly understood; however it appears to be composed of endothelial cells, fibroblasts, adipocytes, macrophages, and extracellular matrix. Bone marrow microenvironment provides supporting stroma and growth factors for haematopoiesis.
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