Lets Recap!

In sexually reproducing organisms, fusion of gametes during fertilisation results in

the formation of a zygote (single-cell organism).
This zygote will undergo multiple rounds of cell division and cell specialisation to
form an embryo (blastocyst) and eventually a foetus.
A foetus would already have developed major organs which are made from
specialised tissues or cells.
What are specialised cells or tissues?
Why is there a need for cell specialisation?

Cell Specialism &

Cell Differentiation
Specialised cells are cells that are structurally
adapted to perform a specific function. These
cells are said to have undergone cell
differentiation.
Cell differentiation means cells become
specialised for a particular function and cannot
be changed into a different type of cell once
the fate has been determined.
In most cases, this process is irreversible.

There are some cells in our body which have

not undergone differentiation and these cells
are known as stem cells.

STEM CELLS
C

Ms Siti Sarah Mohammed

Learning Outcomes
Describe the unique features of zygotic stem cells, embryonic stem cells
and blood stem cells, correctly using the terms totipotency, pluripotency
and multipotency.
Explain the normal functions of stem cells in a living organism, including
embryonic stem cells and blood stem cells.
Discuss the ethical implications of the application of stem cells in research
and medical applications and how human induced pluripotent stem cells
(iPSCs) overcome some of these issues (procedural details of how iPSCs are
formed are not required)

POTENCY OF
STEM CELLS

Types of Potency in Stem Cells

Totipotent
stem cells which have
the ability to
differentiate into any
cell type to form
whole organisms
also pluripotent and
multipotent
E.g. zygote

Pluripotent
stem cells which have
the ability to
differentiate into
almost any cell type
to form any organ
also multipotent, but
not totipotent
E.g. embryo

Multipotent
stem cells which have
the ability to
differentiate into a
limited range of cell
types
neither pluripotent
nor totipotent
E.g. blood stem cell

Human Embryo Development

Cell Differentiation

TYPES OF STEM
CELLS

Embryonic Stem Cell (ESC)

Zygote is a totipotent cell i.e. it has the capability to form an entire organism.
When a zygote divides to form the morula and
then the blastocyst, the inner cell mass (ICM)of
the blastocyst would have already differentiated
into the three layers:
1. Ectoderm: forms the nervous system and the
skin
2. Mesoderm: forms the muscles and
cardiopulmonary system
3. Endoderm: forms the GI tract
ICM layer which was originally totipotent,
subsequently became pluripotent as the embryo
develops.

Embryonic stem cells can also be engineered using DNA from

an adult.

Adult Stem Cell

A type of multipotent
stem cell in adult humans
that is used to replace
cells that have died or
lost its function
It is an undifferentiated
cell present in
differentiated tissue that
are able to renew itself
and specialise into any of
the cell types present in
that tissue
Can be somatic or
germline stem cells
E.g. hematopoietic (blood)
stem cell.

What are the differences between ESC and adult stem cells?
Embryonic Stem
Cells

Adult Stem Cells

Source

Embryo

Adult tissue

Potency

Pluripotent; can
become any cell in
the body

Multipotent; can become only some types of

cell in the body

Cell
culture

Easy to culture thus

can produce large
quantities

More difficult to culture; need to extract

sufficient quantity from adult tissue/cell (in
BM, hematopoietic stem cells is 1 in 15,000
cells)

Risk of
rejection

Unknown

Very low; patients own cells can be used to

culture and then reintroduced into his/her
body

Ethical
Yes
butpreferred
patients need
to consent
before
Regardless
of its cons, ESCs areNo
still
for stem
cell regeneration
Concerns
treatment
can be carried out
therapies.
Why?

USES OF STEM
CELLS

Hematopoietic Stem Cells

Bone marrow contains hematopoietic stem cells (pluripotent) which have the potential to
produce blood and immune cells.
Sufferers of blood- or immune system related diseases e.g. leukemia, may have these
stem cells killed by chemotherapy and radiation and should go for a Bone Marrow
Transplant.
Transplanted BM can repopulate the entire blood
system in the new host
But
procedure for extracting BM cells is invasive.
Alternatively, hematopoietic stem cells also circulate
the bloodstream but in very small quantities (1 in
100,000 cells vs 1 in 15,000 cells in the BM). Easier to
extract but not easy to collect sufficient amount of
cells.

Cord Blood Stem Cells

Harvested from the umbilical cord
of a baby after birth
Cells can be frozen
(cryopreserved) in cell banks
Less likely than to be rejected by
the immune system than BM
stem cells but cord blood must
still be matched to the patient to
be successful
Currently used to treat children with cancerous blood disorders such as leukaemia,
as well as genetic blood diseases like anaemia.
Treatment of adults has so far been more challenging but adults have been
successfully treated with double cord transplants (one cord provides insufficient no.
of cells for adults).

 Guaranteed match for autologous transplant

same donor and recipient

Reduced risk of tissue rejection

A ready supply of stored hematopoietic stem cells
Ease of collection: pain- and risk-free
Cord stem cells are younger and more primitive

$250/ye
ar
for 20 years

faster growth rate and greater tolerance for mismatch

1 in 217 individual uses stem cells for treatment

For full list of diseases treated using stem cells: https://www.cordlife.com/sg/treatable-diseases

Skin Stem Cells

Extracted from the hair follicles in the skin
Used to grow sheets of new skin in the lab for
severe burn patients (third degree burns over
large areas of the body) since 1980s.
But new skin has no hair follicles, sweat glands
or sebaceous (oil) glands, so the technique is
far from perfect and further research is needed
to improve it.
Recently, scientists are growing skin from cord
stem cells.

Mesenchymal Stem Cells (FYI)

Found in the bone marrow and are responsible for bone and cartilage repair. They also
produce fat cells.
Multipotent i.e. can make limited number of types of cells, but NOT all types of cells of the
body.
No treatments using mesenchymal stem cells are yet proven but clinical studies are ongoing.

Limbal Stem Cells

Tissue stem cells taken from
an area of the eye called the
limbus can be used to repair
damage to the cornea.
These cells are taken from the
patient, multiplied in the lab
and transplanted back onto
the patients damaged eye(s)
to restore sight.
The treatment has been shown to be safe and effective in early stage trials.
However, this can only help patients who have sufficient undamaged limbal stem cells
remaining in one of their eyes.

ETHICAL
IMPLICATIONS OF
STEM CELL
RESEARCH

What makes stem cell research so controversial?

Use of adult stem cell is widely accepted but not embryonic
stem cells.
Catholicism: views that every embryo is a potential being hence destroying an
ESC is equivalent to killing a life and manipulating it is seen as sinful i.e. acting
God.
Islam: believes that the inception of life is when the embryo has developed into a
foetus (~4 months after conception) and that as long as use of ESC brings about
more good than harm, it is permissible. Some scholars also highlighted that ESC
has the potential to save lives.
Judaism: believes that the inception of life is when an embryo has been implanted
thus use of ESC for research is permissible if implantation has not taken place.
Similar to Islam, it is strongly encouraged for the ESCs to be used for life-saving
purposes.
Others also believe that it is better to utilise the ESC than to waste by discarding.

How do researchers overcome this?

Use of induced pluripotent stem cells
(iPSCs)
iPSCs are adult cells that have been
genetically reprogrammed to an
embryonic stem cell-like state by being
forced to express genes and factors
important for maintaining the defining
criteria for pluripotent stem cells.
Cells can now be de-differentiated
even if the developmental fates have
been determined.
Engineered tissues which derive from
iPSCs will be a nearly identical match to
the cell donor hence minimising tissue
rejection by the recipients immune
system.

Shinya Yamanaka
Nobel Prize in
Physiology / Medicine
2012
for his discovery of
iPS cells
https://youtu.be/0pXea2D_9OU

FYI

Exposed regions of a chromosome

DNA polymerase can easily access gene
to carry out transcription and translation
Genes get expressed to form polypeptide

Tightly packed regions of a chromosome

DNAP unable to access thus no
transcription nor translation
Genes are NOT expressed hence no
polypeptide formation

So what are these reprogramming factors?

Differentiated
cells
have
heterochromatin regions which carry
genes that are not needed for these
cells to function.
These factors are responsible for
unwinding all heterochromatic regions,
making it possible for all proteins to be
produced once again.
Cells are now de-differentiated and
pluripotent once again (like ESCs),
making it possible for scientists to
induce it to become a cell that he/she
desires.
Researchers are now learning how to
reprogram cells to repair damaged
tissues in the human body.

In Summary
Potency of stem cells
totipotent, pluripotent, multipotent

Types of stem cells

embryonic and adult stem cells

Uses of adult stem cells

hematopoietic, mesenchymal, cord, skin and limbal
stem cells

Ethical implications of stem cell research and

alternatives

By now you should be able to

Describe the unique features of zygotic stem cells, embryonic stem cells
and blood stem cells, correctly using the terms totipotency, pluripotency
and multipotency.
Explain the normal functions of stem cells in a living organism, including
embryonic stem cells and blood stem cells.
Discuss the ethical implications of the application of stem cells in research
and medical applications and how human induced pluripotent stem cells
(iPSCs) overcome some of these issues (procedural details of how iPSCs are
formed are not required)