RED CELL PRODUCTION AND ASSOCIATED PATHOLOGIES
ERYTHROCYTOSIS AND POLYCYTHAEMIA
Mature blood cells are derived from stem and progenitor cells.
The mature cells are found in peripheral blood whereas cells at other
stages of the haematopoiesis are normally found in bone marrow.
The haematopoietic stem cells (HSCs) are rare. These cells can self-renew
or give rise to more differentiated cells when they divide. The HSCs can
be divided into long term and short term cells.
They give rise to common lymphoid (CLP) and common myeloid (CMP)
progenitor cells which are precursors of all lymphoid and myeloid cells
respectively.
The CMP cells give rise to megakaryocyte erythrocyte precursors (MEP)
and granulocyte macrophage precursor (GMP) cells which then give rise to
lineage specific cells such as megakaryocyte (MkP) and erythrocyte (ErP)
precursor cells.
,Differentiation cascade allows amplification of cell number.
As cell progress through the differentiation cascade they progressively
lose the capacity to self-renew and become more differentiated until they
finally become fully differentiated.
Along with this their ability to divide changes significantly. Stem cells are
rare and divide rarely. The progenitor and precursor cells have an
enormous capacity for cell division.
This allows the production of a large number of cells that are required
throughout lifetime in blood. As cells become fully differentiated they lose
the capacity to divide. These cells perform their biological function until
they die and are then replaced by more differentiated cells to maintain
homeostasis.
The earliest restricted erythroid progenitors arise from MEPs and are
characterised by the ability to form BFU-Es (burst forming units) in
semi solid cultures under specific conditions.
The BFU-E is a large colony containing thousands hemoglobinized cells.
BFU-E respond to EPO, stem cell factor (SCF), insulin growth factor 1
(IGF1), corticosteroids.
, They also divide slowly and give rise to rapidly proliferating CFU-Es
(colony forming unit). In the presence of certain factors (eg.
Corticosteroids), BFU-Es undergo extended self-renewal before becoming
CFU-Es. (BFU + CFU – intermediate cells)
The bone marrow microenvironment supports haemopoiesis
These are all components of microenvironment of bone marrow. Ligands
+ receptors interaction supports survival and differentiation of these
intermediate cells.
ERYTHROCYTOSIS AND POLYCYTHAEMIA
Mature blood cells are derived from stem and progenitor cells.
The mature cells are found in peripheral blood whereas cells at other
stages of the haematopoiesis are normally found in bone marrow.
The haematopoietic stem cells (HSCs) are rare. These cells can self-renew
or give rise to more differentiated cells when they divide. The HSCs can
be divided into long term and short term cells.
They give rise to common lymphoid (CLP) and common myeloid (CMP)
progenitor cells which are precursors of all lymphoid and myeloid cells
respectively.
The CMP cells give rise to megakaryocyte erythrocyte precursors (MEP)
and granulocyte macrophage precursor (GMP) cells which then give rise to
lineage specific cells such as megakaryocyte (MkP) and erythrocyte (ErP)
precursor cells.
,Differentiation cascade allows amplification of cell number.
As cell progress through the differentiation cascade they progressively
lose the capacity to self-renew and become more differentiated until they
finally become fully differentiated.
Along with this their ability to divide changes significantly. Stem cells are
rare and divide rarely. The progenitor and precursor cells have an
enormous capacity for cell division.
This allows the production of a large number of cells that are required
throughout lifetime in blood. As cells become fully differentiated they lose
the capacity to divide. These cells perform their biological function until
they die and are then replaced by more differentiated cells to maintain
homeostasis.
The earliest restricted erythroid progenitors arise from MEPs and are
characterised by the ability to form BFU-Es (burst forming units) in
semi solid cultures under specific conditions.
The BFU-E is a large colony containing thousands hemoglobinized cells.
BFU-E respond to EPO, stem cell factor (SCF), insulin growth factor 1
(IGF1), corticosteroids.
, They also divide slowly and give rise to rapidly proliferating CFU-Es
(colony forming unit). In the presence of certain factors (eg.
Corticosteroids), BFU-Es undergo extended self-renewal before becoming
CFU-Es. (BFU + CFU – intermediate cells)
The bone marrow microenvironment supports haemopoiesis
These are all components of microenvironment of bone marrow. Ligands
+ receptors interaction supports survival and differentiation of these
intermediate cells.