formation of cell

1. BY: MRS. GARIMA NAGPAL
Tutor, Pathology
MMU, MULLANA

2. contents
 Introduction
 Hematopoietic growth factors
 Pluripotent stem cells
 Normal sites for hematopoiesis

3.  Is the production,development and
maturation of cellular elements of blood .
heam = blood and
poiesis = production .
Consists of production of erythrocyte ,
leukocyte and thrombocyte .

4. Hematopoietic growth factors
DEFINATION:- Hematopoietic growth
factors regulate the differentiation and
proliferation of particular progenitor cells. .
 These growth factors may act locally near the
site at which these are produced or circulate
in the blood.

5. Hematopoiesis growth factors
TYPES:-
 G-CSF: Granulocyte colony stimulating factor.
 GM-CSF: Granulocyte-Macrophage colony
stimulating factor .
 M-CSF Monocyte colony stimulating factor.
 EPO,Erythropoietin.
 Thrombopoietin.
 Cytokines

6. HEMATOPOIESIS GROWTH FACTORS:
 G-CSF : Stimulate granulocyte production
and primes neutrophils for function.
 GM-CSF : Stimulatory action on granulocyte
and monocyte progenitors
 M-CSF : Activate monocyte progenitors.

7.  EPO,erythropoietin:
Proerythroblast is the earliest morphologically
identifiable erythroid precursor.
.
 TPO,Thrombopoietin:
Regulation of megakaryocyte proferation and
platelets production.

8.  Cytokines:-
IL 1 (Interleukin 1)
IL 3
IL 4
IL 5
IL 6
IL 9
IL 11
SCF (Stem cell factor)
cytokines have no capacity to stimulate cell
proliferation on their own, but are able to bound
with other cytokines.
.

9. Basophil
Eosinophil
RBC
Neutrophil
T Lymphocyte
Monocyte
Platelets
B
Lymphocyte
Pluripotent
Stem Cell
Committed
Stem Cell
CFU-Meg
Lymphoid
Progenitor
Cell
CSCPSC
LPC
MPC
Myeloid
Progenitor
Cell
BFU-
E
CFU-
E
CFU-
M
Colony-forming Unit -
Monocyte. Granulocyte
CFU-
GM
CFU-
G
CFU-
Eo
CFU-
Mast
HEMATOPOIESIS
Growth factors
M-CSF
IL-3,
GM-CSF*
*
*
G-CSF
IL-6
IL-3
SCF
IL-1
*
*
EPO
TPO

10. Pluripotent stem cells:
 Common precursor for all series of cells like
erythrocyte, megakaryocytes, lymphocytes
and granulocytes. The blast cells through in
several stages of division and differentiation
develops into mature cells of each series.

11. Cell hierarchy (Haemopoiesis schematic representation)

12. Normal sites for hematopoiesis:
embryo Till third week- yolk sac
fetal third week–liver ,fourth month :bone maarrow
Birth. : the bone marrow is virtually the sole source of blood
cells
childhood all bone marrow is red and vertically
hematopoietically active.
Adult(18 year age )and above: vertebrae,ribs,sternum,skull and proximal epiphyseal
regions of the humerus and fumer.

13. Stem cells:
In postnatal life, erythrocyte,
monocyte, granulocyte and platelets are normally
produced only in bone marrow. Lymphocyte are
produced in secondary lymphoid organs, as well as
in the bone marrow and thymus gland.

14. ERYTHROPOIESIS
 RBC has to undergo the most changes,
which can be categorized into several
morphological/ stainable stages and into
less easily detected early stages.

15. RBC Precursor Morphology
 Proerythroblast
 Early erythroblast
 Intermediate erythroblast
 Late erythroblast
 Reticulocyte
 Mature RBC

16.  Proerythroblast :
It is one of the largest cell (15-20 microns)in bone
marrow and has a nucleus with stippled chromatin and
1-2 nucleoli. They have blue cytoplasm and are
extremely metabolically active with abundant mRNA
used to manufacture protein.
 Early erythroblast :
The nuclear chromatin condenses, nucleoli are lost and
there is light basophilic cytoplasm. Their size is 14-16
microns.

17.  Intermediate erythroblast:
Reddish tinge in the cytoplasm appears as hemaglobin
production start. Size is 10-14 microns and nucleus is
condensed.
 Late erythroblasts:
The nucleus is densely pyknotic and well haemoglobinised
reddish cytoplasm.Size is 7-10 microns.These cells may
appear in PBF if bone marrow is stressed .

18. Reticulocyte :
Reticulocyte occupy an intermediate position
between nucleated RBCs and mature red cells and
tend to stain somewhat bluer than mature RBCs
on romanowsky stain .Its size is 7-8 microns.
Mature RBC:
Mature RBC has a life span of 100-120 days .They are
anucleated .Their size is slightly small than the small
lymphocyte.Their major roll is to carry oxygen and
carbondioxide.

19. RBC maturation:
Maturation
Stages
Size of cell Nucleus Cytoplasm Mitosis Hemoglobin
Proerythroblast 15-20 um Big, 2-3
nucleoli
Deep basophilic Active Absent
Early (basophilic)
normoblast
14-16 um Small, no
nucleoli
Less basophilic ++ Absent
Intermediate
(polychromatoph
ilic) normoblast
10-14 um Size decreases, Polychromatophilic ++ Start appear
Late normoblast
(orthochromatop
hilic)
7-10 um Nucleus
disappear
Marked increases No Increases
Reticulocyte 7-8 um Absent Acidophilic, little RNA
present
No Increases
Erythrocyte 7.2 um Absent Acidophilic No Fully present

20.  Development of lymphocyte:
The precursors of the lymphocyte in red bone
marrow, during the fetal life from red bone
marrow, about 70% lymphocyte precursors go to
thymus. These are processed and become T-
lymphocyte. And the remaining 30% are B-
lymphocyte. The normal value is 20-30% of the
total WBC’s, life is vary to few hours to years.

21. T Lymphocyte maturation
Pluripotent Stem Cell
common precursor to all of the blood
cells
 Lymphoid Stem Cell:
Daughter cell of the Pluripotent Stem Cell,
this cell divide to produce progenitors to
either B cell or T cell lines.
 T lymphocyte is located in the thymus and
divides to produce mature T cells. The T cell
will induce rapid growth of white blood cells
which help fight infection.

22. B Lymphocyte maturation
Pluripotent Stem Cell
common precursor to all of the blood cells
 Lymphoid Stem Cell
 B Cell progenitor…found in the bone
marrow of higher vertebrates and the Bursa
of Fabricius in birds.
 B Cells when activated will produce
antibodies against particular antigens.

23.  Development of monocyte
Monoblast is the earliest
recognizable cell which develops from myeloid
series (CFU-GM), promonocyte. The nuclei of
the monocyte is kidney shape ,agranulated,
16-18 um in diameter and seen in circulating
blood in 2-8% of total WBC’s and life is 24 hrs.

24. Myeloid Stem Cells
Granulocyte -Monocyte Progenitor cells can
differentiate into monocytes:
Granulocyte -Monocyte Progenitor
MONOCYTE
Macrophage…functions
as antigen presenting cell

25. Development of granulocytes:
 From the colony forming unit–GM,
myeloblast cells are occurs in big sized with
large sized nucleus, in these cells cytoplasm is
non granular.
 Myelocyte cells are smaller in size, contain
round, oval nucleus with large pink cytoplasm.
These cells are further maturation and
differentiate in all granulocyte (neutrophils,
Eosinophils, basophils).

26. Myeloid Stem Cells
Granulocyte -Monocyte Progenitor
BASOPHIL ESINOPHIL NEUTROPHIL

27.  Neutrophils maturation stages are myeloblast to
promyelocyte to N. myelocyte to N. metamyelocyte to N.
band to Neutrophil, multilobed (3-5), very fine granules,
having 10-12 um in size in diameter and concentration is 40-
70% of total WBC’s.
 Eosinophils are bilobed nucleus, fine granules with take
eosin stain, the diameter of the cell is 10-14 um, and in blood
finding is 2-4%, also known as acidophil.
 Basophils are also bilobed nucleus, course granules takes
stain blue, 8-10 um in diameter in size and concentration in
blood is 0-1% of total WBC’s.

28. Thrombopoiesis:
Process in which generation and maturation of
the platelets. Platelets are developed from gaint cells
called megakaryocytes in the bone marrow. A single
megakaryocyte can give rise to about 40-1000
platelets. These cells are produced from
Pleuripotent stem cell CFU-M to
promegakaryoblast megakaryocyte
platelets, are non-nucleated, the normal
life span of cells are 7-14 days in circulation and the
concentration in blood is 1.5 to 4.5 lakhs/cumm.

29. Platelets
Pluripotent Stem Cell
common precursor to all of the blood cells
Myeloid Stem Cells… daughters of
the Pluripotent Stem Cells
Megakaryocyte…fragments into
sub cellular pieces called platelets
Platelets…are blood cells without
nuclei

30. GARIMA NAGPALBY: