BLOOD CELL

FORMATION
(HEMATOPOIESIS)

I. INTRODUCTION
A. Definition
Hematopoiesis is the proliferation of
progenitor cells, which are maintained by
the stem cells and their differentiation into
all the cellular components of blood.
B. Sites of hematopoiesis depend on the
presence of disease and on the developmental state of the individual.
1. Normal conditions originate in the bone
marrow

Some components (e.g., erythrocytes and

platelets) complete their development at
medullary (i.e., bone marrow) sites, whereas
other components (e.g., T and B cells)
complete their development at extramedullary.
Foetus : 0 2 months yolk sac
0 7 months liver, spleen
5 9 months bone marrow
Infants : Bone marrow (practically all bones)
Adults : vertebrae, ribs, sternum, skull,
sacrum, proximal ends of femur

2. Disease
In the presence of disease, extramedullary
sites can serve as primary sites of blood

cell

development.
II. BONE MARROW
A. Stem cells CFU (Colony - Forming Unit)
are found within the BM as the origin of all blood
cells.

~ Blood cells are formed by a process of

differentiation from the least developed stem
cells to highly specialized blood cells. (Table 1)
~ Stem cells :
1. pluripotential stem cells 3 main marrow
cell lines :
a). erythrocytes (red cells)
b). granulocytes monocytes (white cells)
c). thrombocytes (platelets) and probably
lymphocytes (T & B lymp.,plasma cells).

2. Multipotential stem cells myeloid multipotential stem cells and lymphoid multipotential stem cells.
- Myeloid multipotential stem cells :
* CFU-GEMM (CFU-S) CFU granulocytes,
erythrocytes, monocytes and
megakaryocy-

tes; the earliest

detectable myeloid precursor

* CFU-C (CFU-GM) CFU - granulocytes
and monocytes

* CFU-E and BFU-E

- CFU-E CFU erythropoiesis
- BFU-E Burst - Forming Unit - erythroid
committed to erythropoiesis and
precursor of
the CFU-E
- CFU-E and BFU-E are dependent on Epo
* CFU-Meg
- progenitor of megakaryocytes
- derives from CFU-GEMM
- controlled by thrombopoietin
Figure 1. Schematically summarizes the role of the major
progenitor cells of hematopoiesis

Pluripotent
stem cell

CFUGEMM
stem cell

BFUE

Erythroid
Progenitors

Lymphoid

CFUGMEo

CFUEo
CFUMeg

CFUbaso

CFUGM

CFUE
Thymus
CFU-M

CFU-G

B
Red Cells
FIGURE 1.

Platelets

Monocytes

Neutrophils

Eosinophils

Basophils

Lymphocytes

Tabel 1. Some hematopoietic progenitors cells

Term

Required stimulus

Postulated Role

CFU-LM

Multiple GF

Pluripotent stem cell

CFUGEMM
(CFU-S)

GM-CSF, G-CSF,
M-CSF, IL-3

Pluripotent stem cell

CFU-GM
(CFU-C)

GM-CSF, G-CSF,
M-CSF, IL-3

Committed progenitor of
granulopoiesis

BFU-E

Erythropoietin, helper T Committed progenitor of

lymphocytes (IL-1, GM- erythropoiesis (early)
CSF, IL-3, IL-4)

CFU-E

Erythropoietin

Committed progenitor of
erythropoiesis (late)

CFU- Meg

IL-3, GM-CSF, G-CSF.

thrombopoietin

Committed progenitor of
thrombopoiesis

~ Lymphoid multipotential stem cells leave

the bone marrow and complete diff. in
lymph nodes (B cells) and thymus (T cells)
B. Hematopoietic Growth Factors CSF (Colonystimulating factor)
Classification :
a. Non-lineage-specific GF act on pluripotential and multipotential stem cells to
initiate self-renewal and differentiation

~ IL-3 (Multi-CSF) induces the formation

of colonies granulocyte, monocytes,
eosinophils, erythroid cells,megakaryocytes
and mast cells production
~ GM-CSF stimulates granulopoiesis and
macrophage production
b. Lineage-specific GF act on the committed progenitor cells and are involved in the
diff.
and maturation of blood cells in the
later stages of hematopoiesis.

These factors include :

~ Epo stimulates erythropoiesis, mediates
its feed-back control
~ G-CSF inducing formation of granulocyte
stimulates proliferation of some leuke-

and

mic cells

~ M-CSF influencing macrophage prod.

~ Thrombopoietin influencing CFU-mega
2)

(Table

Table 2. Myeloid Hematopoietic Growth Factor

Factor

Major Biological Activities in Vivo

Erythropoietin
(Epo)

Stimulates erythropoiesis. Mediates its feedback

control

GM-CSF

Stimulates granulopoiesis and macrophage

production

G-CSF

Stimulates granulopoiesis and proliferation of

some leukemic cells

M-CSF

Stimulates macrophage production

IL-3 (Multi-CSF) Stimulates granulocyte, monocyte, eosinophils,

erythroid cells, megakaryocyte and mast cells
production

Thrombopoietin Influencing CFU-mega

C.

Lymphokines and monokines

- released by lymphocytes and monocytes
(macrophages) have wide-ranging
h.poietic effects through extensive network
of interaction involving immune responses
to infection and tumor invasion.

- IL (Interleukin) : secreted by lymphocytes,

affect the function of other leukocytes (communication links between leukocytes)
- engage in complex interactions with other IL,
HGF and many other protein such a TNF and
lymphotoxins (Table 3)

Table 3. Lymphoid Hematopoietic Growth Factors

Name

Source

Function

IL - 1

Macrophages, T
and B cells,
fibroblasts

Stimulates growth of T and B cells,

mediates inflammation, inhibits growth of
some cancer cells.

IL - 2 (T

T cells

Binds to receptors on cytotoxic T cells,

promote their growth, stimulates growth of
helper T cells.

IL - 4

T cells, NK cells, Stimulates & regulates growth and diff. of T

mast cells
and B cells, eosinophils and basophils.

IL 5

T cells

Regulates production of eosinophils.

Activates mature eosinophils.

IL - 6

Lymphocytes,
fibroblasts

Promotes macrophage formation.

Stimulates IgG production by B cells.

IL-7

Stromal Cells

Supports long-term survival of B and T

cells in vitro.

IL - 8

Fibroblasts,
vasc. endot.

Enhancement of neutrophil function

cells GF)

(EoGF)

Common General Features of

Hematopoietic Growth Factors
1. All are glycoproteins
2. Regulators of blood cell development and
maturation and enhancers of mature cell
functions, which are active at very low
concentration
3. Active both in vitro and in vivo
4. Produced by cells of many types

5. Usually have both unique and

overlapping specificities
6. Active on both stem (progenitor) cells
and end cells
7. Biologic affects are mediated after
binding to a small number of specific
high - affinity receptors on the surfaces
of target cells

8. Also bind to receptors on some nonhema

- topoietic cells. The significance of this is
unknown
9. Display synergy or additive effects with
other growth factor
10. Also act on neoplastic counterparts of
normal cell type

III. SPLEEN
The chief organ of RES, which also
includes BM, lymph nodes, liver, circulating
monocytes and fixed tissue macrophages.
Its chief role in hematopoiesis occurs in
utero ; its postnatal participation is limited.
Extramedullary hematopoieis in the spleen
occurs in several circumstances

Functions :
Participates in immunologic and phagocytic
activities
Produces stem cells capable of
differentiating along hematopoietic, histiocytic
and fibroblastic cell lines
Play roles in the autoantibody response and
determining blood volume.

IV. EVALUATION OF THE BONE MARROW

1. Indication for a bone marrow aspirate :
Evaluation of decreased numbers of cells
from a single lineage
Ev. of patients with decreased blood cell
counts (bicytopenia or pancytopenia) and
leukemias (stem cell defects & disorder)
Ev. of iron stores and abnormal iron in
erythroid precursor

Diagnosis of tumor involvement

To demonstrate possible infection by
intracellular organism
To investigate an immunologic disorder
Diagnosis of nonhematopoietic diseases
2. Indications for a BM biopsy
Failure to obtain an adequate marrow
aspirate

Evaluation of pancytopenia or bicytopenia

Leukoerythroblastic

findings

in

the

peripheral blood smear

Evaluation of hematologic malignancies
and tumor staging
To defined endpoint of aplasia

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