Download STEM CELLS

Hemopoiesis
Lec.2
Lifespan and production of blood cells
Cell type
Red Cells
Neutrophils
Platelets
Lymphocytes
Approximate
lifespan
Production
rate
cells/day
Production
rate
cells/sec
Production
rate Kg/year
120 days
2 x 1011
2.3 million
7.3
t½ 6 hours
3 x 1010
350,000
10.9
7 days
1 x 1011
1.2 million
4.6
t½ 10 days
1 x 1010
116,000
3.7
Annual total
26.5 Kg
So our body is in a continuous dynamic and a very
rapid cell turnover to be able to live.
HOW ?
It’s the Stem Cell !
HEMOPOIESIS: INTRO
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
Hemopoiesis depends on 3 important
components:
 the bone marrow stroma (Local control)
 the hemopoietic stem and progenitor cells
 the hemopoietic growth factors (Humoral
control)
Interaction of stromal cells, growth
factors and haemopoietic cells
Stromal Cells of BM
Endothelial cells
Fat cells
Fibroblasts
Lymphocytes
Macrophage
STEM CELL THEORY
The dazzling array of 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.
Routes a stem cell can take
self-renew
differentiate
CLONAL HEMOPOIESIS
MULTIPLICATION
COMMITTMENT
COMMITTED
STEM CELL
STEM CELL
MULTIPLICATION
COMMITTED
STEM CELL
CFU: COLONY
FORMING UNIT
CLONAL HEMOPOIESIS:
COLONY FORMING UNIT
(Contd)
(CFU)
MORPHOLOGICALLY
RECOGNIZABLE
MATURE BLOOD CELLS
END CELLS: FINITE LIFE SPAN
INTERMEDIATE
BLAST CELLS
Stages in haemopoietic cell
development
Properties of stem cells
1. Self renewal
2. Hierarchy
3. Extensive proliferative capacity
4. Cell cycle status
5. Surface Markers
6. Interact with microenvironment
Stem Cell Hierarchy
SITES OF HEMOPOIESIS
Yolk
sac
Liver
and spleen
Bone
marrow
–Gradual replacement of
active (red) marrow by
inactive (fatty) tissue
–Expansion can occur
during increased need
for cell production
SITES OF HEMOPOIESIS
Active Hemopoietic
marrow is found,
in children
throughout the:

Axial skeleton:





Cranium
Ribs.
Sternum
Vertebrae
Pelvis
Appendicular
skeleton:
• Bones of the
Upper &
Lower
limbs
In Adults active
hemopoietic marrow is
found only in:
•The axial skeleton
•The proximal ends
of the appendicular
skeleton.
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
Hemopoietic stem cell
Will develop to Blood vessels
will develop to Blood cells
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 produced.
CONTINUED…..
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 stem cells then migrate to the bone marrow
(BM) where hemopoiesis starts and continue
all over the life. In the bone marrow all types
of blood cells are formed which include:
RBCS
Granulocytes: Neutrophils, Eosinophils, Basophils
Lymphocytes
Monocytes and macrophages
Platelets
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
Cell hierarchy (Haemopoiesis schematic
representation)
Haemopoietic growth factors
Haemopoietic growth factors
The haemopoeitic 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, marcrophages 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 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 nine cells into proliferation
Role of growth factors in normal
haemopoiesis
Regulation of Haemopoiesis
Local environmental control
Stromal cell mediated Haemopoiesis
Apoptosis
Haemopoietic
growth factors (Humoral regulation)
Mechanism of apoptosis
Assessment of hemopoiesis
Hemopoiesis can be assessed clinically by;
1- (FBC, CBC= complete blood count) on
peripheral blood.
2- Bone marrow Aspiration also allows
assessment of the later stages of
maturation of hemopoietic cells.
3- Bone marrow Trephine Biopsy
provides a core of bone and bone
marrow to show architecture.
Bone marrow Aspiration
Bone marrow aspiration
Hypercellular
Normocellular
Hypocellular