Mrs.

RUTH TAKYI PERBI

BSc, MPhil 1
OBJECTIVES
 Introduction

 The origin of cell development

 Haematopoietic stem cell

 The site of haematopoiesis

 Haematopoietic growth factors

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 INTRODUCTION
 Haematopoiesis is derived from two Greek words; haima
(blood) and poiesis (to produce something)

 It refers to the formation of blood cellular components

 All blood cellular components are derived from a

haematopoietic stem cells

 In a healthy adult approximately 1011-1012 new blood cells are

produced daily

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 INTRODUCTION
 Another term for haematopoiesis is haemopoiesis

 Haematopoiesis is a continuous, regulated process of

blood cell production that includes;
 Cell Renewal
 Proliferation
 Differentiation
 maturation

 Haematopoiesis starts with stem cell division in which

one cell replaces the stem cell (self‐renewal ) and the other
is committed to differentiation

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HAEMOPOIETIC STEM
CELLS
 Haematopoiesis starts with a pluripotential stem cell

 It can give rise to the separate cell lineages

 This haematopoietic stem cell (HSC) is rare, perhaps 1 in

every 20 million nucleated cells in bone marrow

 Although its exact phenotype is unknown, on immunological

testing the HSC is CD34+ CD38− and negative for lineage
markers (Lin−) and has the appearance of a small or
medium‐sized lymphocyte
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HAEMOPOIETIC STEM
CELLS
 In haematopoiesis there is an intervening step called a
“progenitor cell”

 There are 2 progenitor cells in haematopoiesis;

 Common lymphoid progenitors (CLPs) which give rise to all
lymphoid cells

 Common myeloid progenitors (CMPs) which give rise to all

other blood cells including erythrocytes and platelets.

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HAEMATOPOIETIC STEM CELL

CLP
Lymphocytes
HSC
Granulocytes
CMP erythrocytes
thrombocytes

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Diagrammatic representation of the bone marrow pluripotent cell
and the cell lines that arise from it
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SITE OF HAEMATOPOIESIS
 In the first few weeks of gestation the yolk sac is a transient
site of haematopoiesis

 However, definitive haematopoiesis derives from a population

of stem cells first observed on the AGM
(aorta‐gonads‐mesonephros) region

 The liver, spleen and bone marrow takes over From 6 weeks
until 6–7 months of fetal life

 The liver and spleen are the major haematopoietic organs and
continue to produce blood cells until about 2 weeks after birth
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SITE OF HAEMATOPOIESIS
 The bone marrow becomes the most important site from 6–7
months of fetal life

 During normal childhood and adult life the marrow is the

only source of new blood cells

 The developing cells are situated outside the bone marrow

sinuses

 Mature cells are released into the sinus spaces, the marrow
microcirculation and so into the general circulation

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SITE OF HAEMATOPOIESIS
 The placenta also contributes to fetal haematopoiesis

 In infancy all the bone marrow is haematopoietic but during

childhood there is progressive fatty replacement of marrow
throughout the long bones

 So then in adult life haematopoietic marrow is confined to

the central skeleton and proximal ends of the femurs and
humeri

 Even in these haematopoietic areas, approximately 50% of

the marrow consists of fat

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SITE OF HAEMATOPOIESIS
 The remaining fatty marrow is capable of reversion to
haematopoiesis

 In many diseases there is an expansion of haematopoiesis

down the long bones

 Moreover, the liver and spleen can resume their fetal

haematopoietic role („extramedullary haematopoiesis‟).

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 SITE OF
HAEMATOPOIESIS

Fetus Yolk sack (0-2 months)

Liver, spleen (2-7 months)

Bone marrow (5-9 months)

Infants Bone marrow (all bones)

Adults Vertebrae, ribs, sternum, skull,

sacrum and
pelvis, proximal ends of femur

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 HAEMOPOIETIC GROWTH
FACTORS
 These are glycoprotein hormones that regulate the
proliferation and differentiation of haematopoietic progenitor
cells

 They may act locally by cell–cell contact or circulate in

plasma

 The growth factors may cause cell proliferation but can also
stimulate differentiation and maturation

 It can prevent apoptosis and affect the function of mature

cells

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HAEMOPOIETIC GROWTH
FACTORS
 Growth factors share a number of common properties and act
at different stages of haematopoiesis

 Stromal cells are the major source of growth factors except

for erythropoietin, 90% of which is synthesized in the kidney,
and thrombopoietin, made largely in the liver

 Two or more factors may synergize in stimulating a

particular cell to proliferate or differentiate

 The action of one growth factor on a cell may stimulate

production of another growth factor 17
 HAEMOPOIETIC GROWTH
FACTORS
 SCF and FLT3 ligand (FLT3‐L) act locally on the pluripotential
stem cells and on early myeloid and lymphoid progenitors

 Interleukin‐3 (IL‐3) and granuloctye–macrophage

colony‐stimulating factor (GMCSF) are multipotential growth
factors with overlapping activities

 G‐CSF and thrombopoietin enhance the effects of SCF, FLT‐L,

IL‐3 and GM‐CSF on survival and differentiation of the early
haematopoietic cells

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A diagram of the role of growth factors on normal
haematopoiesis

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 THANK YOU
QUESTIONS / COMMENTS ?

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