HEMATOPOIESIS

- LADI
ANUDEEP
ISM-IUK
 The process of formation of blood
cells i.e. RBC’S, WBC’S and platelets
is called as haematopoiesis and the
sites where it occurs are known as
hemopoietic tissues or organs (bone
marrow, liver, spleen)
 Cells responsible to do function of
hemopoiesis are first seen in yolk sac
of embryo in third week of embryonic
development and these cells are
known as hematopoietic stem cells
 DEFINITION OF STEM CELL
 Cells capable of asymmetrically
dividing, one group of cell is
responsible for production of well
differentiated products and another
group of cell is responsible to maintain
the original population if stem cell and
shows a character called as self-
renewal
 Hematopoietic stem cells also take origin in mesoderm of
aorta, mesoderm of gonads and mesoderm of meso-
nephrons
 Hematopoietic stem cells present in yolk sac migrate to other
parts like liver, spleen and bone marrow
 The hematopoietic stem cells present in yolk sac at third
week of embryo migrate to liver at around third month of
foetal life
 So, around third month of embryo the liver gets populated
with these stem cells and become a major organ for
haematopoiesis-DOMINANT MIGRATION
 Some hematopoietic stem cells also migrate to lymph nodes,
spleen –MINOR MIGRATION
 Liver , lymph nodes and spleen continue as hematopoietic
organs until birth
 After birth, liver stops its hematopoietic activity because
around 4 th month of foetal life migration of stem cells from
liver, lymph nodes and spleen takes place to bone marrow
 So at time of fourth month of foetal life, hemopoiesis takes
place in bone marrow
 Bone marrow is permanent residence for hematopoietic stem
cells
 At time of birth, all hematopoietic stem cells are limited to
bone marrow and bone marrow will be active
 Active bone marrow is called as RED BONE MARROW and
inactive bone marrow is called as YELLOW BONE
MARROW
 Yellow bone marrow is accumulated with fat cells, so it is
yellow in colour and red bone marrow is highly vascular and
rich in hematopoietic stem cells
 For new born baby, all bone marrow are red and as age
increases red bone marrow is active only in membranous
bones
 Up to puberty , all most all bone marrow is red and at age of
puberty and after puberty hematopoiesis stops in large
bones and is limited to axial skeleton, proximal ends of
 In new born, if hematopoiesis is going on outside
of bone marrow i.e. in liver, spleen and lymph
nodes it is called as EXTRA MEDULLARY
HEMATOPOIESIS
 If there is need of excessive hematopoietic
activity, yellow bone marrow has a capacity is to
be reactivated and converted into red bone
marrow ( seen in severe hemolysis)
 When there is excessive hematopoiesis, red
bone marrow expands too much into outer bone
table o skull and in x-ray outer bone table is not
visible and only picules are visible and this
condition is known as HAIR ON END
APPEARANCE
 Bone marrow has reserve function—when in
need it can increase erythropoietic activity
significantly
Process Of Hematopoiesis
 It starts with first generation stem cell called as
Pleuripotent stem cell and the term pleuripotent stem
cell refers that they have a potency to convert into
many different types of tissues
 Pleuripotent stem cells divides into two different types of
multipotent stem cells
 Multipotent stem cells are cells that have a capacity to
self renew by dividing and to develop into multiple
specialised cell types present in a specific tissue or
organ
 The two types of multipotent stem cells are: 1) cells
related to lymphoid system are known as Common
Lymphoid Stem Cells and 2) the cells related to
myeloid system are known as Common Myeloid Stem
Cells
 Myeloid system refers to all blood cells other than
lymphoid cells( lymphocytes)
 1) COMMON LYMPHOID STEM CELLS
 Multipotent stem cells
 Further divided into three types of committed lymphoid stem
cells:
 A) PRO-NK CELLS: which multiply and differentiate, when
enter into blood circulation called as Natural killer Cells
 These are not B or T lymphocytes
 B) PRO-T CELLS: which multiply and differentiate and pre
mature cells which are derivatives of pro-T cells enter into
peripheral circulation and through circulation enters into
thymus gland where maturity takes place and after maturation
come back to peripheral circulation as T-Lymphocytes
 T-lymphocytes are called as CD-3 positive cells
 T-Lymphocytes are divided into 2 types: > cells which are CD-
3 and CD-4 positive are called as T-HELPER CELLS and are
again divided into 2 types T-H1 and T-H2
 Major function of T-H1 is that they produces gamma-
interpherons, TNF(tumour necrotic factor) and they act on
monocytes which in presence of T-H1 converted into active
macrophages, epithelioid cells and giant cells
 Major function of T-H2 is that they stimulate B-Cells to get
converted into PLASMA CELLS by the cytokines, IL-4 and
IL-5 produced by it
 IL-4 work as B cell growth factor and IL-5 work as B cell
differentiation factor-----these help B cell to convert into
plasma cells which produce antibodies
 T-H1 help in cellular immunity and T-H2 help in humoral
immunity
 > Cells which are CD-3 and CD-8 positive cells called as T-
CYTOTOXIC CELLS which also take an active part in cellular
immunity
 C) PRO-B CELLS: which get multiplied and differentiated into
B-CELLS which get converted into plasma cells in action of
TH-2 cells to produce anti bodies
 2) COMMON MYLOID STEM CELL
 Multipotent stem cells
 Divided into types of committed stem cells:
 A) ERYTHROID MEGAKARYOID BASOPHILIC STEM
CELL
 Has a potential to go into morphologically recognisable
precursors of 3 types:
 > CFU ERYTHROID SYSTEM
 Gets converted into erythroblast and passes to different
stages to form reticuloblast which later on produces Mature
RBC
 This is a morphologically recognisable precursor cell for
erythropoiesis
 > CFU MEGAKARYOID SYSTEM
 Gets converted into megakaryoblast which passes on
different stages and enter into blood circulation as
PLATELETS
 Morphologically recognisable precursor cell for
megakaryopoesis
 > CFU BASOPHILS SYSTEM
 Gets converted into basoblast which passes
on different stages and enter peripheral
circulation as basophils
 On surface of basophils there are surface
receptors for IgE antibodies
 Pleuripotent cells are also responsible for
production of MAST CELLS and have
receptors for IgE anti-bodies and play a major
role in type-1 hypersensitivity
 This is morphologically recognisable
precursor cells for basophils
 B) GRANULOCYTE MONOCYTE
STEM CELLS
 It is divided into 2 types of
morphologically precursor cells:
 > CFU FOR GRANULOCYTE: after
series of divisions myloblast is formed
and enters into peripheral circulation
as Neutrophils
 Neutrophils has granules of red and
blue colour
 >CFU FOR MONOCYTE: convert into Monoblast after series
of divisions and enters into peripheral circulation as
Monocytes
 Monocytes also have granules but these are agranulocytes
 Monocytes when shifted to tissue where inflammation occurs
are called as inflammatory macrophages
 Monocytes when shifted to CNS during early phase of
development are called as Microglial cells
 Monocytes when shifted to liver are called as Kupfer cells
 Monocytes when shifted to lung are called as Alveolar
Macrophages
 When monocytes shifted to spleen and lymph nodes are
called as Dendritic cells or Histiocytes
 Monocytes when shifted to kidney are called as Mesengial
cells
 Monocytes under skin are called as Langerhan cells
 Monocytes that are shifted to bone Osteocytes
 C) EOSINOPHILOID STEM CELLS
 Produce precursor cell called as
EOSINOPHIOLOBALST and enter blood
circulation to give rise to Eosinophills
 Eosinophills have red granules
 The condition in which the stem cells cannot
multiply with enough speed to maintain RBC’S,
WBC’S, and platelets number in peripheral
circulation is called as Aplastic Anaemia , so
blood cells number is reduced in blood
 In patient suffering with aplastic anaemia, bone
marrow becomes hypocelluar and in peripheral
blood pancytopenia is seen
 When stem cells are proliferating excessively,
this condition is called as LEUKEMIAS
PECULIARITIES OF BONE
MARROW
 Bone marrow provide unique environment for proliferation
and differentiation of these stem cells and precursor cells
 Bone marrow is rich in stromal cells which support
hematopoietic process
 Stromal cell are capable of concentrating a lot of soluble
factors( growth and differentiation factors) like erythropoietin,
thrombopoietin, stem cell colony stimulating factors, IL-3 etc
 IL-3 are responsible for stem cell proliferation
 Stromal cells have cell to cell interaction with hematopoietic
cells and directs their differentiation
 Soluble factors like erythropoietin, thrombopoietin,
granulocyte monocyte colony stimulating factors and
granulocyte colony stimulating factor are synthesised by
genetic recombination techniques and are used commercially
 Bone marrow provide homing in tendency for stem cells
 The bone marrow stromal cells have special surface
adhesion molecules and these stem cells love those
adhesion molecules
 Under certain conditions are induced to produce Hemangioblasts
cells which on differentiates to give endothelial cells
 Bone marrow stem cells can also produce non-hematopoietic stem
cells like liver cells, biliary duct cells, myocardial cells, skeletal
muscle cells, fully matured NEURONS , glial cells
 Bone marrow is made of network of sinusoids which are lined by
single layer of endothelial cells coated by basement membrane but
is discontinuous
 Hematopoiesis will be going on in the spaces between sinusoids(
also called as interstitium of bone marrow)
 Megakaryoblast have a finger like processes which are extended
through sinusoids and when blood is flowing through sinusoids these
finger like processes are broken, enter into circulation and are
called as Platelets
 Erythroblast present in cytoplasm differentiates and become
progressively smaller in size
 As erythroblast differentiates nucleus becomes smaller and
disappears and size decreases
Peculiarities Of Erythropoiesis
 Erythroblast present in cytoplasm has large
nucleus with blue cytoplasm and
differentiates to become progressively small
in size
 As erythroblast differentiates, nucleus
becomes smaller, it gets condensed and
disappears, cell size decreases
 Changes From Pro-erythroblast to Mature
RBC
 Size gradually decreases
 First cytoplasm is basophilic but
progressively basophilic nature disappears
and eosinophilic nature appears
 Nucleus disappears and condenses
 For nuclear maturation and condensation, there is
requirement of VITAMIN B12 and FOLIC ACID
 If there is severe deficiency of B12 and folic acid, there
is haemoglobin production but there is no nuclear
condensation
 When there is severe B12 or folic acid deficiency, there
is formation of megaloblast which is larger size
normoblast which are having eosinophilic cytoplasm
and immature nucleus and causes megaloblastic
macrositic anaemia
 And there is requirement of iron for haemoglobinisation
of cytoplasm
 So, for erythropoiesis there is need of B12 and folic acid
for nuclear maturation and there is need of iron for
haemoglobinisation of cytoplasm and there is also
requirement of Growth Hormone and amino acids for
normal cell metabolic activities