Constituents of Blood and Bone

marrow and regulation of

hematopoiesis
Dr Deepti Joshi
AIIMS Bhopal

Cells of Blood

Peripheral smear

Blood cells are derived from bonemarrow

Common ancestor of all blood cells

All blood cells are progeny of a single cell type
(Hematopoeitic Stem cell or HSC)
Processes involved in production of various
types of blood cells is Hematopoeisis
Hematopoeisis included self-renewal of stem
cells,commitment to specific lineages and
maturation of lineage committed progenitors
to functional blood cells.

Sequence of events
Stem cells
Progenitor cells (recognized by culture
techniques)
Recognizable proliferating marrow precursors
Mature cells

Progenitor Cells of erythroid series:

BFU-E
Earliest defined erythroid progenitor.
It is called a burst because it of its ability to create a "burst" on
semisolid media, i.e. a colony consisting of several hundred to
thousand cells in 10 -14 days.
Requires
IL-3
Granulocyte-macrophage colony stimulating factor
Erythropoietin

For proliferation, prevention of apoptosis, & differentiation to

morphologically recognizable erythroid precursors

10-20 % are in cycle at a time

Found in significant nos. in peripheral blood

CFU-E
BFU-E differentiates into colony forming unit
erythroid.
Identified in vitro by smaller colonies (50200 cells)
that grow in 3 to 5 days.

However, EpoR density & Epo dependency

gradually as progenitor cells mature, culminating at
the level of the CFU-E.

BFU-E and CFU-E cannot be identified by

microscopy

Changes in properties during differentiation of erythroid

progenitors

Subdivisions of Hematopoeisis
Lymphopoeisis
Myelopoeisis
Granulopoeisis
Monocytopoeisis
Erythropoeisis
Megakaryopoeisis

 HSCs reside in bonemarrow but under stress

can get tranferred to other organs like liver
and spleen (Extramedullary hematopoeisis)
HSC can give rise to non-hematopoeitic cells
Turnover and replenishment of the
hematopoeitic system continues through out
the life
Regulation of hematopoeisis is a complex
process.

Sites of hematopoeisis
Embryonic

Yolk sac

5th gestational week

Rudimentary liver

7th week onward

Liver is the dominant site until the

30th gestational week

6th month onward

Cavities of long bones

At birth

All bone cavities are actively engaged in

erythroid production, the hepatic
(fetal) phase of erythropoiesis comes to
an end

Some RBC production can be found in thymus, spleen, or lymph nodes,

these sites are never dominant. Foci of hematopoietic activity detected within
the embryo around the developing aorta (in the paraaortic-splanchnopleura [PSp] & the aorta/gonad/mesonephros [AGM] area.

Structure of hematopoietic organ

Anatomic structure (3 D organization of different tissue types and their component

cells)
Stroma
Hematopoeitic progenitor cells and their progeny (Erythroid, Myeloid, and
megakaryocyte series)

Bone-marrow anatomy
Largely anatomic features
of hematopoietic organs
are unknown
Functions of the cells of
venous sinuses within the
marrow understood
Venous structure is a
complex maze of sinuses
that drain into central
veins
Hematopoeitic
progenitors differentiate
outside these sinuses

 Formed by a continuous layer of endothelial

cells which on extra-luminal side are covered
by fenestrated adventitial reticular cells
EC provide selective exit of mature blood cells
from the marrow into the blood stream.

Hematopoeitic stem cell niche

Bone-marrow stromal niche supports HSC
activity
Two types of HSC niche: Osteoblastic niche
and vascular niche
Marrow stromal niche maintains the
quiescence of the HSC and releases
committed progenitor cells while vascular
niche harbours the progenitor cells before
releasing them into circulation

Stroma
Important for Stem cell renewal
Homing of HSC to the hematopoeitic organs
Egress of mature hematopoeitic cells from bone
marrow into blood
various cells as well as the extracellular
macromolecules that occupy the hematopoeitic tissue
along with the hematopoeitic cells
Includes
myofibroblasts,adipocytes,macrophages,plasma
cells,lymphocytes,endothelial cells,stem cells
It constitutes the microenvironment in which the cells
grow and differentiate

Morphologically identifiable erythroid

series

Morphologically identifiable Myeloid

series

Normal granulocyte precursors in

the bone marrow

Metamyelocyte & Band form

Megakaryoblasts
Megakaryoblasts are
the precursors of the
megakarycytes.
They may show
cytoplasmic blebbing.

Megakaryocyte

Regulation of hematopoeisis
Local environmental control.
Role of haemopoeitic growth factors (Humoral
regulation)
Apoptosis
Complex interaction between stromal
cells,growth factors and hematopoeitic cells
Adhesion molecules
Transcription factors

Hematopoeitic growth factors

GM-CSF
M-CSF
Erytropoeitin
Thrombopoeitin
Cytokines
C-kit 3 and FLT-3 (act on early progenitors)

Transcriptional factors
GATA1 and PU.1 (Myeloid commitment)
GATA 1and fog1 (erythroid)
PU.1 (Common lymphoid )

Erythropoeisis
Process of development of red cells from
precursor cells is known as erythropoeisis.
Collectively, the progenitor & adult RBCs
are termed the erythron to reinforce the
idea that they function as an organ.
Divided into two phases-EPO dependent
and EPO independent

Thank You.