stem cells

1. STEM
CELLS
Dr.Abhinav Golla MBBS,MD Pathology
Medicure Diagnostics & research
center, vijayanagar colony ,
Hyderabad,Telangana

2. INTRODUCTION
 During development stem cells give
rise to all the various differentiated
tissues ; in the adult organism
 They – replace damaged cells
maintain tissue population
as individual cells within them
undergo replicative senescence due
to attrition of telomeres .

3.  There is homeostatic equilibrium
between the replication , self renewal
and differentiation of stem cells and
the death of the mature , fully
differentiated cells .
 The dynamic relationship between
stem cells and terminally
differentiated parenchyma is
particularly evident in the
continuously dividing epithelium of
the skin.

4.  Thus stem cells at the basal layer of the
epithelium progressively differentiate as
they migrate to the upper layer of the
epithelium before dying and being shed.

6. PROPERTIES OF STEM
CELLS
 Stem sells are categorised by two important
properities
1) self renewal – which permits stem cells
to maintain their number.
2) asymmetric division- in which one
daughter cell enters a differentiation
pathway and give rise mature cells. While
other remain undifferentiated and retains
the self renewal capacity.

7. TYPES OF STEM CELLS
 Embryonic stem cells (ES cells)
 Tissue stem cells ( adult stem cells
)
Hematopoietic stem cells

8. EMBRYONIC STEM CELL
 ES cells are the most undifferentiated cells
 Present in inner cells mass of the blastocyst
 Have virtually limitless self renewal capacity
 They can give rise to every cell in the body
 They are thus said TOTIPOTENT STEM
CELLS.
 These cells can be maintained for extended
period with out differentiating
 They can be induced under apropiate culture
condition to form specialised cells of all the
germ cell layers ( neurons , cardiac muscle,
liver cells and pancreatic islet cells )

10. TISSUE STEM CELL
 They are found in intimate association with
the differentiated cells of a given tissue
 They are protected within specialized tissue
microenvironment called STEM CELL
NICHES .
 Soluble factors and other cells within niches
keep the stem cells quiescent until there is a
need for expansion and differentiation of the
precursor pool.

11.  Adult stem cells have a limited repertoire
of differentiated cells that they can
generate.
 Although adult stem cells can maintain
tissue with high cell turn over ( skin , git )
and low cell turn over ( heart , brain ) ,
these cells in any given tissue can usually
only produce cells that are normal
constituents of the tissue.

12. NICHES
 Brain – neural stem cells – sub
ventricular
zone and dentate gyrus.
 Skin – bulge region of the hair follicle .
 Cornea – limbus
 Small intestine – base of the crypt,
above
paneth cell
 Liver – oval cells – canals of Hering .

17. HEMATOPOIETIC STEM
CELLS
 They continuously replenish all the cellular
elements of the blood as they are consumed
.
 They can be isolated directly from bone
marrow as well as from peripheral blood
after administration of certain CSF that
induce their release from the bone marrow
niches .

18.  Although rare , hematopoietic stem cells
can be purified to virtual homogeneity
based on cell surface markers and ability
to give rise to blood cell of lineages
 Clinically these stem cells can be used to
repopulate marrows depleted after
chemotherapy or to provide normal
precurssors to correct various blood cell
defects .

20. HSC
 Blood cell progenitors first appear during
third week of embryonic development of the
yolk sac.
 Definitive HSC arise several weeks later in
the mesoderm of the intra embryonic
aorta/gonads/meso-nephros region.
 During 3 rd month of embryogenesis they
migrate to liver which becomes the chief site
of blood cell formation until shortly before
birth .

21.  HSC also take up residence in the fetal
placenta this pool of HSC is of certain
physiologic relevance.
 HSC harvested at birth from umbilical cord
blood are being used increasingly in
therapeutic hematopoietic stem cell
transplantation.
 By 4th MONTH of development HSC shift
location yet again taking up residence in
the bone marrow .

22.  By birth marrow throughout the skeleton
is hematopoietically active and hepatic
hematopoiesis dwindles to a trickle,
persisting only in widely scattered foci
that become inactive soon after birth.
 Until puberty, hematopoietically active
marrow is found throughout the skeleton ,
but soon thereafter it becomes restricted
to axial skeleton.
 Thus ,in normal adults, only about half of
the marrow space is hematopoietically
active.

23.  HSCs have two essential properties that are
required for the maintenance of
hematopoiesis :
Pluripotency
Capacity for self-renewal.
 Pluripotency refers to ability of single HSC to
generate all the mature blood cells.
 When a HSC divide atleast one daughter cell
should self renew to avoid stem cell
depletion.
 Self – renewal divisions occur in the
specialised niches in the marrow in which
stromal cells and secretory factors nuture
them.

24.  HSC are not sessile.
 Under conditions of marked stress (
severe anemia ) they are mobilized from
the bone marrow and appear in the
peripheral blood .
 HSC used in transplantation are now
collected from peripheral blood of donor
treated with granulocyte colony
stimulating factor (G-CSF).

25. STEM CELL ROLE IN
CANCER
 Limitless replicative potential is the key
factor for cancers.
 At least some cells in all cancers are like
stem cell like ; these cells are sometimes
referred to as cancer stem cells .
 These may arise through transformation of a
normal stem cell or through acquired genetic
lesions that impart a stem like state on a
more mature .

26. STEM CELL ROLE IN
REGENERATION
 The regeneration of injured cells and tissues
involve cell proliferation , which is driven by
growth factors and is critically dependent on
the integrity of the extracellular matrix, and
by the development of mature cells from
stem cells.

27. TAKE HOME MESSAGE
 Stem cells are totipotent
pleuripotent
mutlipotent
unipotent.
 IHC markers of HSC – CD34, CD133,
CD117(C-
KITRECEPTOR),CD90,CD59+,CD110.
 Stem cells are used in tissue regeneration
treating diseases
transplantation

28.  Stem sells are categorised by two important
properities
1) self renewal – which permits stem cells to
maintain their number.
2) asymetric division- in which one daughter
cell enters a differentiation pathway and give rise
mature cells. While other remain undifferentiated
and retains the self renewal capacity.
 Properties of stem cells can be illustrated in
vitro using methods such as clonogenic assay

29.  Cord blood is used for treating many
diseases like stroke , parkinsons disease ,
alzheimers disease, liver and heart
diseases, diabetis mellitus , leukemia ,
GVHD ,etc.
 Stem cells are preserved in cryobank
 Located in guargaon , chennai, banglore ,
kolkata, mumbai.