Bone Marrow and
Hemopoiesis
DR ONYANGO K
01/03/2021
Objectives
Types of bone marrow and functions.
Cellular architecture of bone marrow.
Importance of myeloid-erythroid ratio in bone marrow.
Define haemopoiesis and name the sites of haemopoiesis
in different stages.
Differences between medullary and extramedullary
haemopoiesis.
Types of stem cells and properties.
Outline the steps of different series (erythropoiesis,
leucopoiesis and thrombopoiesis) of haemopoiesis.
Regulation of haemopoiesis.
Bone marrow
Bone marrow is the site of normal hemopoiesis
after birth.
Hemopoiesis (or hematopoiesis) describes the
formation of blood cells, which is an active
process that must maintain normal number of
blood cells in peripheral blood and also should be
able to respond to the increased demands in
situations like hemorrhage or infections.
During fetal life, hemopoiesis mainly occurs in the
spleen and liver, and subsequently in red bone
marrow present in the medullary cavity of all
bones.
From childhood, red marrow is progressively
replaced by fat tissues (yellow marrow).
Normal hemopoiesis in adults is restricted to
vertebrae, sternum, ribs, clavicles, pelvic bones,
skull and ends of humerus and femurs.
Contains a range of hemopoietic precursor cells
and a storage pool of mature cells for their release
into peripheral circulation.
All blood cells are derived from the pluripotent
stem cells, referred to as hemopoietic stem cells
(HSCs).
HSCs sustain life long production of all blood
lineages.
HSCs provide homeostasis of blood cells through
their ability to generate the hundreds of millions of
red cells, white cells and platelets needed every
day.
Types of marrow
There are three types of bone marrow: red
marrow, yellow marrow and white marrow.
Red marrow
The red marrow is the active marrow and is red in
colour.
It consists of many blood vessels that contain
sinusoidal capillaries
(vascular sinuses), and the marrow stroma .
Marrow stroma: The marrow stroma consists
principally of a network of sinuses that originate
at the endosteum from cortical capillaries and
terminate in the collecting vessels that enter the
systemic circulation.
Hematopoiesis takes place in the intersinus
spaces
The trilaminar sinus wall contains three
components:
1. Endothelial cells
2. Thin basement membrane
3. Adventitial reticular cells.
The bone forming cells are present between the
sinusoidal capillaries.
The adventitial reticular cells are fibroblasts
capable of transforming into adipocytes (fat cells).
Endothelium and reticular cells are the sources of
cytokines that profoundly influence haemopoiesis.
All types of precursor cells (blast cells, progenitor
cells, megakaryocytes) are present in the bone
marrow trabeculae.
Red cells are produced from the erythroid ‘nests’.
Red bone marrow is present in almost all bones of
the body at birth.
With advancement of age red marrow is replaced
by fatty tissue and slowly becomes inactive.
At the age of 20–30 years, red marrow of long
bones cease to produce cells, and active marrow
is limited to the membranous bones like skull
bones, vertebrae, ribs, sternum and pelvic and
pectoral girdles.
Yellow marrow
The yellow marrow contains less blood vessels
and more fat cells and fibro-fatty tissue.
The yellow marrow does not participate in
hemopoiesis.
Fat cells replace hematopoietic cells in the bones
of hands, feet, legs and arm at about age of 20
years.
Fat occupies 50% of the space of red marrow in
adult and further fatty degeneration continues
slowly with aging.
Yellow marrow can revert back to hemopoietically
active red marrow when prolonged demand
persists as occurs in chronic hemolytic anemia.
White Marrow
In very old individuals, a gelatinous
transformation of fat to a mucoid material occurs
in bone marrow.
This type of marrow in elderly persons is called
white marrow.
Haemopoiesis
Hemopoiesis is the process of formation
(development, maturation and release) of blood
cells.
This is also called hematopoiesis.
Blood cells are continuously destroyed in the
body.
Therefore, replacement of blood cells is also a
continuous phenomenon and is an essential part
of homeostasis of blood cells.
Sites and Stages of
Hemopoiesis
Location of hematopoiesis depends on the stage of
hematopoiesis.
During intrauterine life, hematopoiesis occurs first in
the yolk sac, and later in the liver and spleen.
After birth, hematopoiesis is confined to bone
marrow.
The environment in these organs (yolk sac, liver,
spleen and bone marrow) where hematopoiesis takes
place is called hematopoietic microenvironment.
Hematopoiesis occurs in three stages: mesoblastic,
hepatic and medullary.
Mesoblastic stage
Mesoblastic stage is the stage of development of
blood cells in the yolk sac and non-yolk sac
regions during embryonic stage of intrauterine
life.
Yolk sac contains cells with multilineage
differentiating capabilities that start functioning
as early as second week of gestation.
There are also few non-yolk sac regions that
participate in hematopoiesis.
Important among them are paraaortic
splanchnopleura (PSP) and aorta-gonad
mesonephros (AGM) regions.
PSP region gives rise to B-cell progenitors and
AGM region contains pleuripotent stem cells.
Early lymphoid precursors have also been
identified in the day-8 yolk sac.
Lymphohematopoieti stem cells have been
detected in vivo in the 9th day yolk sac.
Hepatic stage
During second trimester of pregnancy,
hemopoiesis takes place in the liver and spleen.
This is hepatic stage.
In liver, hematopoiesis starts as early as 5th
week of gestation, which reaches its peak in
5th month and ceases at birth.
In spleen, hematopoiesis occurs mainly in the
second trimester and the degree of hematopoiesis
is quite less than that in the liver.
Hematopoiesis does not occur in liver and spleen
during post-natal life (after birth).
When the demand for blood cells is more than
the rate of production, hematopoiesis does occur
in liver and spleen.
Intrauterine haemopoiesis
Medullary stage
Formation of blood cells in the bone marrow is
called medullary hemopoiesis.
Marrow cavities in the bone appear as early as
5th month of fetal life, and soon they
become hemopoietic.
In initial phase, bone marrow is the exclusive site
for granulocytic and megakaryocytic proliferation,
during which erythropoietic activity is confined to
liver.
Erythropoiesis in bone marrow occurs effectively
towards the end of third trimester of pregnancy
and then continues throughout life.
After birth, hemopoiesis stops in liver and gets
confined only to the bone marrow.
When hemopoiesis occurs in liver and spleen in
postnatal life, is called extramedullary
hemopoiesis.
Extramedullary hemopoiesis after birth is always
non-physiological.
Rate of medullary
haemopoiesis
Bone marrow is one of the largest organs in the
human body.
It produces about 6 billion cells (2.5 billion red
cells, 2.5 billion platelets and 1 billion
granulocytes) per kg of body weight per day in
adolescents and adults.
The rate of production is adjusted to the needs of
day-today life.
Bone marrow is the sole site of erythropoiesis in
human beings.
In long bones, active marrow regresses rapidly
after first decade of life and ceases to produce
cells between 20–30 years of life.
Haemopoiesis continues to occur in active marrow
of vertebrae, pectoral and pelvic girdles, ribs,
sternum and skull.
With age the degree of haemopoiesis also
decreases in these bones.
Steps of haemopoiesis
Hematopoiesis occurs in the bone marrow from
hematopoietic stem cells .
The mother hematopoietic stem cell is the
pluripotent stem cells (PPSC), also called as
hemocytoblast.
PPSC is the multilineage stem cell capable of
producing two important groups of stem cells.
These are myeloid stem cells and lymphoid cells.
Lymphoid stem cells are unipotent stem cells
(UPSC) that produce only lymphocytes, whereas
myeloid stem cells are pluripotent in naturethat
from a group of different progenitor cells that are
meant to produce red cells, granulocytes,
monocytes and platelets.
Bone marrow contains two types of cells: stem
cells and progenitor cells.
Stem cells develop into progenitor cells.
Stem cells
Properties
Stem cells in the bone marrow have two important
properties:
self renewal and differentiation.
Self Renewal
This is the property of duplicating themselves.
Renew themselves and therefore physiologically they do not
die and at the same time they proliferate into different
lineage of cells.
Due to self renewal, the bone marrow never goes out of
stock for stem cells.
Stem cell reserve in bone marrow remains always adequate.
Differentiation
This is the property of developing into specific
lineage of cells.
Due to the property of differentiation, stem cells
differentiate into progenitor cells of various cell
lines.
Different cell lineages are formed from stem cells
that give rise to specific blood cells.
Myeloid Stem Cells
Myeloid stem cells are pluripotent (tri-lineage) in
nature that give rise to three types of different
progenitor cells.
These are erythroid progenitors that form erythroid
series, the granulocytic progenitors that form
granulocytes (neutrophil, eosinophil, and basophil),
monocytic progenitors form monocytes, and
megakaryocytic progenitors that form platelets.
Lymphoid Stem Cells
Lymphoid stem cells are unipotent stem cells (UPSC)
that produce only cells of lymphocyte series.
Progenitor cells
Progenitor cells develop from stem cells.
Progenitor cells form colony forming units (CFUs)
that give rise to different types of blast cells.
Myeloid stem cells differentiate into CFU-
GEMM, i. e. CFU for granulocyte, erythrocyte,
megakaryocyte and monocyte.
CFU-GEMM develops into three major CFUs
CFU-E: CFU-E is the CFU for erythroid series that
form proerythroblast, which in turn develops into
precursor cells of erythroid series.
CFU-GM: CFU-GM is the multilineage CFU that in
turn forms CFU for granulocytes (CFU-G) and CFU
for monocytes (CFU-M).
CFU-G develops into myeloblast that differentiates
into three lineage of granulocytes (neutrophil,
eosinophil, and basophil).
CFU-M develops into monoblast that differentiates
into monocyte.
CFU-Mega: CFU-Mega differentiates into
megakaryoblast that in turn forms platelets.
Types of haemopoiesis
Hemopoiesis is broadly divided into three types:
erythropoiesis, leucopoiesis and thrombopoiesis.
Erythropoiesis is the development of red cells,
leucopoiesis is the development of leucocytes and
thrombopoiesis is the development of
thrombocytes (platelets).
The PPSC diffentiates into five major blast cells
that give rise to five different cell lines.
The proerythroblast that forms erythroid
series for final development of red cells.
The myeloblast that differentiates into three
lineages of granulocytes series (neutrophil,
eosinophil, and basophil).
The monoblast that differentiates into
monocytes.
The lymphoblast that develops into
lymphocytes
The megakaryoblast that finally forms
platelets.
Cell lineage and Cytokines (HGFs)
Erythroid-BFU Erythropoietin, IL3, IL4 and GM-CSF
Erythroid-CFU Erythropoietin
Neutrophil-Macrophage GM-CSF
Macrophage CSF-1, IL1 and IL8
Neutrophil G-CSF
Eosinophil IL5 and IL3
Megakaryocyte IL3, IL1, IL6, IL4, GM-CSF and LIF.
Basophil-Mast cell IL3, and GM-CSF
B lymphocytes IL7, IL4, IL5 and SCDC
T lymphocyte IL2, erythropoietin and GM-CSF
Regulation
Hemopoiesis is regulated by various cytokines.
Cytokines that influence development of blood
cells are called hemopoietic growth factors
(HGFs).
As they stimulate development of CFU, they are
popularly called colony stimulating factors (CSFs).
Many of them are nonspecific, influencing more
than one cell line ,whereas few are very specific in
their actions.
Erythropoietin: It is secreted from kidney and
stimulates development of erythrocyte precursors
.
Interleukins (IL): There are many interleukins,
IL1 to IL11.
IL5 controls eosinophil development, IL2 and
IL4control lymphocyte development, IL1 and IL2
control monocyte-macrophage development.
Colony stimulating factors: There are three major
groups of CSFs: M-CSF, G-CSF and GM-CSF.
M-CSF controls development of monocyte
precursors, G-CSF controls growth of granulocyte
precursors and GM-CSF promotes proliferation of
both granulocytes and monocytes.
Other growth factors: Colony stimulating factor 1
(CSF 1) that influences macrophage development,
leukemia inhibitory factor (LIF) that controls
growth of megakaryocyte and stroma cell derived
cytokine (SCDC) that influences B cell
differentiation.
