Haemopoiesis Flashcards
Haemopoiesis
The formation, development and differentiation of blood cellular components
-Erythropoiesis:
formation of red blood cells
-Myelopoiesis:
formation of granulocytes and monocytes
-Lymphopoiesis:
formation of lymphocytes
-Thrombopoiesis :
formation of platelets.
THE HAEMOPOIETIC SITES at different stages of development
• Mesoblastic phase
– 2nd week - 3rd month
– Cell clusters in yolk sac
• Hepatic phase
– 2nd – 7th month
– Mainly liver with supplementation from spleen
• Myeloid phase
– 6th month – adult – Red bone marrow
Discuss bone marrow sites from infancy to adulthood
In infancy all the bone marrow is haemopoietic.
▪ During childhood, there is progressive fatty replacement of marrow throughout the long bones.
▪ In adult life, haemopoietic marrow is confined to the central skeleton and proximal ends of the femurs and humeri.
STAGES IN HAEMOPOIETIC CELL DEVT
Lineage Selection
↓
Physical Maturation
↓
Functional Maturation
↓
Cell Death
What is the THE HAEMOPOIETIC STEM CELL
• Starting point of Haemopoiesis.
• Morphologically resembles a small
lymphocyte.
• Exact phenotype unknown,
Characteristics of a stem cell
• Has the capacity for self reproduction (self renewal) that is required to maintain cell production for a normal lifetime.
• Pluripotent i.e can generate different types of tissues (Stem Cell Plasticity).
• Humans possess 2 x 10^4 stem cells
▪ One stem cell can produce about 106 mature blood
▪ Daily blood cell formation is 4 x 10^11 cells : 2 x 10^11 RBCS, 1 x 10^11 WBCs and 1 x 10^11 Platelets.
cells after 20 divisions.
▪ When required, the stem cells are able to increase production of any of the cell line
Discuss the Bone marrow
• It provides a suitable environment for the stem cells to survive, grow and develop.
• It composed of stromal cells and microvascular network.
• Stem cells are able to move around the body, and are found in small numbers in the periphery.
Discuss the stromal cells of bone marrow
Bone marrow: The stromal cells
• Consist of adipocytes, fibroblasts, endothelial cells and macrophages.
• Form extracellular matrix composed of collagen, glycoproteins and glycosaminoglycans.
• Secrete growth factor for stem cell survival
Discuss the stromal cells of bone marrow
Bone marrow: The stromal cells
• Consist of adipocytes, fibroblasts, endothelial cells and macrophages.
• Form extracellular matrix composed of collagen, glycoproteins and glycosaminoglycans.
• Secrete growth factor for stem cell survival
Discuss PROGENITOR CELLS and what they are characterized by
• Cell differentiation occurs from the stem cells via haemopoietic progenitors.
• They are formed as a result of the loss of one or more developmental potentials of the HSC,
• Characterized by :
- Loss of pluripotency
- Lack of capacity for self renewal
- Higher fraction of cells traversing the cell cycle
. There are 2 types : Multipotential and Committed.
• They are either myeloid or lymphoid progenitors
• Are not visible morphologically
• Their existence can be demonstrated by in-vitro culture techniques
• Very early progenitors: Assayed by culture on bone marrow stroma
• Late progenitors: Assayed on semi-solid media
Progenitors develop into
The Precursors
• The morphologically identifiable blood cells • Eventually develop to become mature cells
Stages of erythropoiesis
Proerythroblast.
Basophilic normoblast.
Polychromatic Normoblast
Orthochromatic Normoblast.
Reticulocyte.
Erythrocyte (fully mature red blood cell).
REGULATION OF HAEMOPOIESIS is controlled by:
Haemopoietic Growth Factors
A balance between cell production and cell death is needed
• When necessary, production of cells may exceed the cell death i.e. haemorrhage.
Haemopoietic Growth Factors
• Glycoprotein hormones that regulate the proliferation and differentiation of the progenitor cells.
• May act locally at site of production/ circulate in plasma.
• Can cause cell proliferation, differentiation, maturation, prevent apoptosis and affect function of normal cells.
The major sources of growth factors
– T-lymphocytes,
– monocytes (and macrophages)
– stromal cells
• The kidneys produce erythropoietin • The liver produces thrombopoietin
Examples of Haemopoietic growth factors
Haemopoietic growth factors
• GM-CSF
• Granulocyte-Macrophage colony stimulating factor
• M-CSF
• Macrophage colony stimulating factor
• Erythropoietin
• Erythropoiesis stimulating hormone
• Thrombopoietin
• Stimulates megakaryopoiesis
Cytokines
•IL(Interleukin) 1, IL 3, IL 4, IL 5, IL 6, IL 9, IL 11
• 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 synergise with other cytokines to recruit other cells into proliferation
General characteristics of Haematopoeitic Growth factors
– Can act at very low concentration
– Affect more 1 lineage
– Show synergistic action
– Act on neoplastic cells equivalent to normal cells
– Act hierarchically
– Produced by many cells
– Usually active on stem/ progenitor cells and on functional end cells
– Multiple actions
Growth factors: Clinical applications
• Treatment of anaemia
• Treatment of neutropenia
• Treatment of thrombocytopaenia
• Haemopoietic stem cell transplantation
