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.
Hemopoiesis
Stem Cell Theory
All the blood cells are produced by the bone marrow.
They all come from a single class of primitive mother cells called as:
PLURIPOTENT STEM CELLS.
These cells give rise to blood cells of:
Myeloid series: Cells arising mainly from the bone marrow.
Lymphoid series: cells arising from lymphoid tissues.
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”
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.
Properties of stem cells
Self-renewal
Hierarchy
Extensive proliferative capacity
Cell cycle status
Surface Markers
Interact with microenvironment
Sites of hemopoiesis
Yolk sac
Liver and spleen
Bone marrow
–Gradual replacement of active (red) marrow by inactive (fatty) tissue
–Expansion can occur during the increased need for cell production.
Sites of hemopoiesis
|
Active Hemopoietic marrow is found, in children throughout the: Axial skeleton: Cranium Ribs. Sternum Vertebrae Pelvis |
|
Sites of Hemopoiesis
In the embryo
2 week old embryo, hematopoiesis begins in yolk sac.
THE 1ST CELL TO BE PRODUCED IS erythrocytes
By 2 month old fetus, granulocyte and megakaryocyte production.
4th month, lymphocytes production.
5th month, monocytes were produced.
In the 3rd to 7th month of fetal life Hemopoietic stem cells will migrate to the liver and spleen, where hemopoiesis starts there and hemopoiesis is still mainly erythropoietic in nature, with minimal granulopoiesis.
The bone marrow (BM)
The lifespan of blood cells
|
Cell type |
Approximate lifespan |
|
Red Cells |
120 days |
|
Neutrophils |
t½ 6 hours |
|
Platelets |
7 days |
|
Lymphocytes |
t½ 10 days |
Extramedullary Hemopoiesis
When required, yellow marrow can be replaced by red marrow.
Liver & spleen can aslo resumed.
This will multiply the production by 6.
Remark that Hemopoiesis within the marrow is called intramedullary or medullary hemopoiesis.
Hematopoietic Inductive Microenvironment
The stromal matrix plays an important role in presenting growth factors and nutrients to developing blood cells.
The most immature cells have receptors which bind them to proteoglycan molecules on the matrix and to receptors on the stromal cells (i.e. macrophages, fibroblasts, fat cells and endothelial cells)
There are lineage specific regions ( "niches" ) which provide the molecular basis for homing of transplanted stem cells.
The unique supportive microenvironment stem cell niche - regulates proliferation and differentiation - supports survival and inhibits apoptosis
Similar principles apply to malignant stem cells in myeloid leukemias.
The sinusoids are lined with specialized endothelial cells which play an important role by producing factors which regulate growth and differentiation.
Stromal Cells of BM
Endothelial cells
Fat cells
Fibroblasts
Lymphocytes
Macrophage
Haemopoietic growth factors
The haemopoietic growth factors are glycoprotein hormones that regulate the proliferation and differentiation of haemopoietic progenitor cells and the function of mature blood cells.
T lymphocytes, monocytes, macrophages and stromal cells are the major sources of growth factors except for erythropoietin, 90% of which is synthesized in the kidney and thrombopoietin, made largely in liver.
Haemopoietic growth factors
GM-CSF
Granulocyte-Macrophage colony stimulating factor
M-CSF
Macrophage colony stimulating factor
Erythropoietin
Erythropoiesis stimulating hormone
(These factors have the capacity to stimulate the proliferation of their target progenitor cells when used as a sole source of stimulation)
Thrombopoietin
Stimulates megakaryopoiesis
Haemopoietic growth factors
Cytokines
IL 1 (Interleukin 1)
IL 3
IL 4
IL
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 nine cells into proliferation.
Stem Cells
Stem Cells: undifferentiated cells that give rise to all of the bone marrow cells.
Only 0.5% of all marrow nucleated cells.
Multipotential precursors.
High self-renewal – give rise to daughter stem cells that are exact replicas of the parent cell.
Not morphologically distinguishable At any time, the majority of stem cells (95%) are out of the cell cycle (they are in G0 mode/phase, also called quiescent).
Progenitor cells of the BM
Stem cells which undergo differentiation.
Limited self-renewal ability.
Multipotential but Gradually they become unilineage or committed progenitor cell.
~3% of total nucleated hematopoietic cells of bone marrow
Progenitor cells of the BM
Form colonies of cells in semisolid media in vitro – described as colony forming units (CFU).
CFU-GEMM (granulocytic, erythrocytic, monocytic,megakaryocytic,CFU-GM,CFU-Mk, etc. )
Survival and differentiation of progenitor cells influenced by growth regulatory glycoproteins, called cytokines – include interleukins, colony stimulating factors
Morphology of stem cells and progenitor cells
Stem cells & progenitor cells are not recognized morphologically but all look like small mononuclear lymphocytes.
Maturing blood cells
Majority of cells (>95%)
lose adherence receptors, become deformable.
migrate through cytoplasm of lining endothelial cell to enter sinusoids.
Platelets are the exception.
Megakaryocytes form part of the sinusoidal wall. They form long processes of proplatelets which fragment into nascent platelets.
Apoptosis
Regulated physiological cell death
Homeostasis
Morphological evidence
Enzymatic digestion of DNA and cell disintegration
Caspases
Endonuclease
Two major pathway of activation of caspases
Membrane signalling
Cytochrome c release
Granulopoiesis
Monocytes
Lymphopoiesis
Immunologically competent cells
Primary lymphoid organs
Bone marrow
Thymus
Secondary lymphoid organs
Lymph nodes
Spleen
Lymphoid tissues
Lymphocytes
B and T lymphocytes
NK killer cells
Thrombopoiesis
Summary
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