Hemo: Referring to blood cells
Poiesis: “The development or production of”
The word Hemopoiesis refers to the production & development of all the blood cells
2. HAEMATOPOIESIS
Hemo: Referring to blood cells
Poiesis: “The development or production of”
The word Hemopoiesis refers to the production
& development of all the blood cells:
Erythrocytes: Erythropoiesis
Leucocytes: Leucopoiesis
Thrombocytes: Thrombopoiesis.
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3. Conti…
• Granulopoiesis (or granulocytopoiesis) is
haematopoiesis of granulocytes.
• Megakaryocytopoiesis is haematopoiesis
of megakaryocytes
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4. Overview
• All cellular blood components are derived
from haematopoietic stem cells.
• In a healthy adult person, approximately 1011–
1012 new blood cells are produced daily in
order to maintain steady state levels in the
peripheral circulation
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5. Stem cells
These cells have extensive proliferative capacity and
also the:
Ability to give rise to new stem cells (Self Renewal)
Ability to differentiate into any blood cells lines
(Pluripotency)
They grow and develop in the bone marrow.
The bone marrow & spleen form a supporting system,
called the
“hemopoietic microenvironment”
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6. STEM CELLS: Types
Pluripotent Stem cells:
Has a diameter of 18 – 23 μ.
Giving rise to: both Myeloid and Lymphoid series of cells
Capable of extensive self-renewal.
Myeloid Stem cells: Generate myeloid cells:
Erythrocytes
Granulocytes: PMNs, Eosinophils & Basophils.
Thrombocytes.
Lymphoid Stem cells: Giving rise only to:
Lymphocytes: T type mainly.
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7. Hematopoietic stem cells (HSCs)
• Haematopoietic stem cells (HSCs) reside in the medulla of
the bone (bone marrow) and have the unique ability to give
rise to all of the different mature blood cell types and
tissues.
• HSCs are self-renewing cells: when they proliferate, at least
some of their daughter cells remain as HSCs, so the pool of
stem cells does not become depleted.
• The other daughters of HSCs (myeloid and lymphoid
progenitor cells), however can commit to any of the
alternative differentiation pathways that lead to the
production of one or more specific types of blood cells, but
cannot self-renew. This is one of the vital processes in the
body.
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8. Rules of Normal Cell Proliferation
Routes a stem cell can take
self-renew
differentiate
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9. Rules of Normal Cell Proliferation
Symmetric cell division Asymmetric cell division
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10. Sites of Hemopoiesis
• Hemopoiesis starts as early as yolk sac development.
• 2-3 weeks after fertilization 3 layers are developed (ecto,
meso, and endoderm)
• Hemoangioblast which is derived from the
mesoderm
Hemoangioblast
Endothelial stem cell
Will develop to Blood
vessels
Hemopoietic stem cell
will develop to Blood
cells
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11. Sites of Hemopoiesis
• . In children, hematopoiesis occurs in
• 1-femur
• 2-tibia
• . In adults, it occurs mainly in
• 1-Pelvis
• 2-cranium
• 3-vertebrae
• 4-Sternum
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13. Sites of Hemopoiesis
• As development progresses, blood formation occurs in
the spleen, liver and lymph nodes.
• When bone marrow develops, it eventually assumes the task of
forming most of the blood cells for the entire organism.
• Maturation, activation, and some proliferation of lymphoid cells
occurs in secondary lymphoid organs (spleen, thymus, and lymph
nodes).
• In some cases, the liver, thymus, and spleen may resume their
haematopoietic function. This is called extramedullary
haematopoiesis.
• During fetal development, since bones and thus the bone marrow
develop later, the liver functions as the main haematopoetic organ.
• Therefore, the liver is enlarged during development.
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14. Factors involve in hemopoiesis
• Several transcription factors have been isolated that
regulate differentiation along the major cell lineages.
• PU.1 (Transcription factor) commits cells to the myeloid
lineage
• GATA-1 (Erythroid transcription factor) has an essential
role in erythropoietic and megakaryocytic differentiation.
• The proliferation and self-renewal of these cells depend
on stem cell factor (SCF).
• Glycoprotein growth factors regulate the proliferation and
maturation of the cells that enter the blood from the
marrow, and cause cells in one or more committed cell
lines to proliferate and mature.
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15. Factors involve in hemopoiesis
• Three more factors that stimulate the production
of committed stem cells are called “colony-
stimulating factors(CSFs)”
– granulocyte-macrophage CSF (GM CSF)
– granulocyte CSF (G-CSF)
– macrophage CSF (M-CSF).
• These stimulate much granulocyte formation
and are active on either progenitor cells or
end product cells.
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17. Order of blood cell formation
1) STEM CELLS
2) Progenitor cells may be mutli-potential,
bi-potential or uni-potential
3) Precursor cells, or also called maturing
cells
4) Terminally differentiated cells Mature
cells
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19. Hematopoiesis
• In order to form blood cells, pluripotent stem cells in red
bone marrow produce myeloid stem cells and lymphoid
stem cells.
• Myeloid stem cells begin their development in red bone
marrow and give rise to red blood cells, platelets,
monocytes, neutrophils, eosinophils, and basophils.
• Lymphoid stem cells begin their development in red bone
marrow but complete it in lymphatic tissues; they give rise
to lymphocytes.
• Although the various stem cells have distinctive cell identity
markers in their plasma membranes, they cannot be
distinguished histologically and resemble lymphocytes.
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20. Hematopoiesis
• During hemopoiesis, some of the myeloid stem
cells differentiate into progenitor cells.
• Other myeloid stem cells and the lymphoid stem
cells develop directly into precursor cells
(described shortly).
• Progenitor cells are no longer capable of
reproducing themselves and are committed to
giving rise to more specific elements of blood.
• Some progenitor cells are known as colony-
forming units (CFUs)
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21. Hematopoiesis
• In the next generation, the cells are called
precursor cells, also known as blasts.
• Over several cell divisions they develop into the
actual formed elements of blood. For example,
monoblasts develop into monocytes, eosinophilic
myeloblasts develop into eosinophils, and so on.
• Precursor cells have recognizable microscopic
appearance
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25. Hematopoietic regulating factors
• Several hormones called hemopoietic growth factors regulate the
differentiation and proliferation of particular progenitor
cells.
• Erythropoietin (e-rith-ro ¯-POY-e-tin) or EPO increases
the number of red blood cell precursors. EPO is produced primarily
by cells in the kidneys that lie between the kidney tubules
(peritubular interstitial cells).
• With renal failure, EPO release
slows and RBC production is inadequate.
• Thrombopoietin or TPO is a hormone produced by the liver that
stimulates the formation of platelets (thrombocytes) from
megakaryocytes.
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26. Hematopoietic regulating factors
• Several different cytokines regulate development of different
blood cell types.
• Cytokines are small glycoproteins that are typically produced by
cells such as red bone marrow cells, leukocytes, macrophages,
fibroblasts, and endothelial cells.
• They generally act as local hormones (autocrines or paracrines.
• Cytokines stimulate proliferation of progenitor cells in red bone
marrow and regulate the activities of cells involved in nonspecific
defenses (such as phagocytes) and immune responses (such as B
cells and T cells).
• Two important families of cytokines that stimulate white blood cell
formation are colony-stimulating factors (CSFs) and interleukins.
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27. ERYTHROPOIETIN
• A hormone produced by the Kidney.
• A circulating Glycoprotein
• Nowadays available as Synthetic Epoietin
• Acts mainly on CFU – E.
• Increases the number of:
– Nucleated precursors in the marrow.
– Reticulocytes & Mature Erythrocytes in the
blood.
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28. Hematopoietic Growth Factors
• Thrombopoietin
• is a glycoprotein hormone produced
mainly by liver and kidney that regulates
the production of platelets in bone
marrow.
• It stimulates the production and
differentiation of Megakaryocytes
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29. Hematopoietic Growth Factors
GM-CSF: (Granulocyte Marophage-colony stimulating
factor)
Produced by fibroblasts, stromal cells,T.lymphocytes and
endothelial cells.
• Stimulate progenitors for granulocytes, monocytes and
erythrocytes
G-CSF:
• LMW glycoprotein
• Stimulates proliferation and maturation of granulocyte
precursors.
• Produced by stromal cells, monocytes, macrophages,
and endothelial cells.
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30. Hematopoietic Growth Factors
• M-CSF
• Secreted by stromal cells, macrophages and
fibroblasts.
• Potent stimulator of macrophage function and
activation as it increases the expression of
MHC.II antigen on macrophages.
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31. Thank you For Attention
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