Haemopoiesis is the term used for the production of blood cells within the human body. Embryonic haemopoietic stem cells-mesenchymal cells are present in yolk sac. After 12 week fetal liver and spleen becomes the main site for the haemopoiesis. From week 20, bone marrow starts to become important and by the time of birth it is the main haemopoietic organ. There is gradual replacement of active (red) marrow by tissue inactive (fatty) marrow. Expansion can occur during increased need for cell production. Bone marrow is found mostly in the axial skeleton and inner spongy bone which is in form of the holes where blood production takes place. It is a highly organized and regulated organ which is the source of our blood and immune system.
All blood cells arise from “mother” (stem) cells and are self-renewing plus safe from any harm. They are pluripotent. Blood production is highly regulated by messages from the body (e.g. erythropoietin from kidney); microenvironments produce specific cells; cytokines (SCF, IL3) and growth factors (G-CSF). Every day 1013 myeloid cells must be produced. In steady state the number of cells which are required is equal to the body weight. All these cells are derived from the stem cells. Stem cells are relatively few in number, comprising 0.01% to 0.05% of the marrow cells.
Stem cells self- renewal process occurs normally in G0 phase of cell cycle. The capacity for self-reproduction is vastly in excess of that required to maintain cell production for normal lifetime. As cells increase in number they differentiate as well. These cells are of multipotentiality meaning that they have the capacity to generate cells of all the lymphohaemopoietic lineages.
Progenitor cells are developmentally-restricted cells. They encompasses from immediate progeny of stem cells to differentiation cells committed to one lineage. These cells become progressively more restricted in their differentiation and proliferation capacity. Late progenitor cells eventually restricted to one cell lineage only.
Regulation of Haemopioesis
The regulation of haemopoiesis takes place as there should be a balance between cell production and cell death except at the times of requirement. Cells in the different tissues of the body can signal the need of different levels of cell production e.g anoxic conditions lead to production of erythropoietin. The control of cell death by apoptosis is being increasingly acknowledged to be of critical importance. Three factors contribute to this regulation : interaction of stromal cells, growth factors and haemopoietic cells; local and humoral regulation of haemopoiesis with haemopoietic growth factors.
The haemopoietic growth factors include granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF), erythropoietin (erythropoiesis stimulating hormone) and thrombopoietin which stimulates megakaryopoiesis. These factors have the capacity to stimulate the proliferation of their target progenitor cells when used as a sole source of stimulation. Others include : cytokines i.e. IL 1 (Interleukin 1), IL 3,IL 4,IL 5,IL 6,IL 9,IL 11 and TGF-β, SCF (Stem cell factor, also known as kit-ligand). Cytokines have no (e.g. IL-1) or little (SCF) capacity to stimulate cell proliferation on their own, but are able to synergize with other cytokines to recruit nine cells into proliferation.
Erythropoiesis is the formation of erythrocytes with the lifespan – 120 days. They are non-nucleated, biconcave discs which require Fe, B12, folate & other elements for development. Their production regulated by Erthyropoietin. In developing from the stem cell, the RBC has to undergo the most changes, which can be categorized into several morphological/stainable stages and into less easily detected early stages. They continue to grow till the final reticulocyte stage which is an RBC released to the blood, but still with a network of blue ribosomal material persisting amongst the hemoglobin.