C3.4: stem cells

Question 1

describe the unique features of stem cells, including zygotic stem cells, embryonic stem cells and blood stem cells (lymphoid and myeloid), correctly using the terms:
totipotency (e.g. zygotic stem cells)
pluripotency (e.g. embryonic stem cells)
multipotency (e.g. lymphoid and myeloid stem cells).

Answer 1

A stem cell is an unspecialized and uncommitted cell from the embryo, fetus, or adult that under certain conditions, has self–renewal capability by reproducing itself for long periods or, in the case of adult stem cells, throughout the life of the organism, and can differentiate whereby unspecialized cells give rise to specialized cells that make up the tissues and organs of the body.
possess large nuclear to cytoplasmic ratio.
Thus, stem cells can (a) replenish their own population and to (b)
generate cells that travel down various differentiation / developmental pathways.

Totipotent stem cells:
MASTER CELLS of the body as they have the ability to give rise to all cell types that make up an organism.
They consist only of zygotic stem cells.
They exist as the fertilized egg (zygote) and the first few cells produced when the zygote divides rapidly by mitosis to form a compact ball of cells called morula. The zygote marks the earliest stage of totipotency.
In mammals, such cells have the potential to differentiate into any cell type in the adult body AND any cell of the extra-embryonic membranes (e.g. placenta).
Occur at the earliest stage of embryonic development; before the blastocyst stage
(Formed immediately upon fertilization, up to first 5 days after fertilization)

Pluripotent stem cells:
These cells descend from totipotent stem cells. They have the ability to give rise to types of cells that develop from the three germ layers (mesoderm, endoderm, and ectoderm) from which all the cells of the body arise.
They do not have the potential to make differentiated cells that form the extra-embryonic membranes (e.g. placenta).
The only known sources of human pluripotent stem cells are those isolated and cultured from inner cell mass of early human embryos and from fetal tissue that was destined to be part of the gonads.
(Formed from 5 to 7 days after fertilization)
EG: Embryonic stem cells

Multipotent stem cells:
descend from pluripotent stem cells and can differentiate into many cell lines within a specific type of tissue. Adult stem cells (e.g blood stem cells, lymphoid and myeloid) are examples of multipotent stem cells.
These are stem cells that can only differentiate into a limited number of cell types.
They are more specialized than totipotent and pluripotent stem cells. For example, the bone marrow contains multipotent stem cells that give rise to all the cells of the blood (red blood cells and white blood cells) but not to other types of cells.
Multipotent stem cells are found in adult animals
(Formed after 7 days upon fertilization)
upon accumulation of sufficient mutations, can produce a clone of cancer cells

Question 2

explain the normal functions of stem cells in a living organism, including embryonic stem cells and blood stem cells (lymphoid and myeloid).

Answer 2

Types of stem cells:
Committed stem cells:
Committed stem cells are those that have a more limited pathway of development compared to pluripotent cells and are destined to produce a specific group of cells
can give rise to more specifically committed stem cells or generate what are called progenitor cells

Progenitor cells:
The intermediate cell is called a precursor or progenitor cell. Progenitor or precursor cells in fetal or adult tissues are partly differentiated cells that divide and give rise to differentiated cells.
Characteristics:
usually shows some evidence of differentiation, although the process is not complete until the fully differentiated cell has been formed.
is committed to a limited number of pathways of differentiation/ development.
is more limited in developmental pathways than a multipotent stem cell.

Asymmetric division and symmetric division of stem cells:
Symmetric: produces 2 genetically identical cells (eg 2 stem cells or 2 progenitor cells)
asymmetric division: Produces one stem cell and a progenitor cell with limited self-renewal potential.
significance: mitotic division of stem cells (1) preserves a population of undifferentiated cells while (2) steadily producing a stream of differentiating cells

Embryonic stem cells:
Embryonic stem cells (ESCs) are derived from embryos
isolated from the inner cell mass (ICM) of the blastocyst — the stage of embryonic development when implantation occurs. ESCs are extracted from frozen surplus 2-5 day pre-implantation embryos fertilised in vitro. These surplus embryos are embryos that are not used for clinical treatment by patients undergoing in vitro fertilisation procedures, and therefore would be discarded. Instead of being discarded, these embryos are voluntarily donated with the informed consent of the donor.
Harvesting ESCs from human blastocysts is controversial because it destroys the embryo, which could have been implanted to produce another baby (but often was simply going to be discarded).

Embryonic Germ Cells (cultured cells in vitro):
can be isolated from the precursor to the gonads in aborted fetuses.
Properties:
Capable of undergoing an unlimited number of symmetrical divisions without differentiating (long-term self-renewal).
Exhibit and maintain a stable, full (diploid), normal complement of chromosomes (karyotype). An ESC has 2 complete sets of chromosomes.
Pluripotent ESCs can give rise to differentiated cell types that are derived from all three primary germ layers of the embryo (endoderm, mesoderm, and ectoderm).
Capable of developing into all fetal tissues during development. (Mouse ES cells maintained in culture for long periods can still generate any tissue when they are reintroduced into an embryo to generate a chimeric animal.)
Clonogenic i.e. a single ESC can give rise to a colony of genetically identical cells, or clones, which have the same properties as the original cell.
Unlike adult stem cells, they are easy to obtain in pure and can be cultivated in large numbers.
Fates of ESCs in a developing embryo
Inner cell mass, ICM, (2 layer disc) forms -> distinguishes cells from each other in terms of their relative positions, other than the inside and outside of the morula. -> continues to develop to form embryo and form a 3 layered disc called primary germ layers, resulting in a 3 layered structure called primordial embryo aka gastrula.
The layer nearest the amniotic cavity is the ectoderm; the inner layer, closer to the blastocyst cavity is the endoderm. Shortly after, a third layer, the mesoderm, forms in the middle.

Blood stem cells:
Hematopoietic (blood-forming) stem cell (HSC)
Multipotent
constantly being generated in the bone marrow where they differentiate into mature types of blood cells
Primary role: replace blood cells derived from the mesoderm in the embryo.
These cells colonize a number of definitive blood-forming sites that include the fetal liver, thymus, spleen and bone marrow.

Multipotent/ hematopoietic stem cells in the red marrow of bones, particularly ribs, vertebrae, breastbone and pelvis -> myeloid progenitor cell (MPC) and lymphoid progenitor cell (LPC) -> erythroid and myeloid lineages derived from common MPC, lymphoid lineage derived from common (LPC)

Lymphoid lineage:
Produces a type of white blood cells, called lymphocytes, which include the two antigen-specific cell types of the immune system, the B and T lymphocytes. Lymphocytes function for specific adaptive immune responses.
B lymphocytes
White blood cells that come from the bone marrow.
make antibodies and help fight infections. Also called B cells.
Develop in the bone marrow
T lymphocytes
White blood cells that attack virus-infected cells, foreign cells, and cancer cells. T lymphocytes also produce a number of substances that regulate the immune response. Also called T cells.
Develop in the thymus from precursors that originate from the multipotent stem cells in the bone marrow and migrate from the bloodstream into the thymus
Both B and T lymphocytes undergo a further terminal differentiation after they encounter antigens.

Myeloid lineage:
Gives rise to the rest of the white blood cells which all derive from the bone marrow in adults.
They include eosinophils, neutrophils, basophils (collectively known as granulocytes or polymorphonuclear leukocytes), mast cells, and monocytes.
Leukocytes are mobile units of the body’s immune system. They function as:
defence against pathogen invasion by phagocytosis,
identification and destruction of cancer cells that arise within the body,
the “clean-up crew” to remove / phagocytize debris from dead / injured cells during wound healing / tissue repair.

ERYTHROID LINEAGE:
Yields the red blood cells, or erythrocytes; and the megakaryocytes, which give rise to blood platelets.
Erythrocytes function mainly to transport gases (oxygen and carbon dioxide) in the blood.
Blood platelets are for blood clotting functions.

Question 3

properties of stem cells

Answer 3

Unspecialised
does not have any tissue-specific structures that allow it to perform specialized functions.
However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells via specialization / differentiation.

STEM CELLS ARE CAPABLE OF DIVIDING AND RENEWING THEMSELVES FOR LONG PERIODS:
stem cells may replicate many times (proliferation)
After proliferation, if the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal by mitotic divisions.

STEM CELLS CAN GIVE RISE TO SPECIALIZED CELLS VIA DIFFERENTIATION:
Both the signals (a) inside and (b) outside cells trigger stem cell differentiation.
Internal Signals: During differentiation, differential gene expression occurs when certain genes become activated and other genes become inactivated in an intricately regulated fashion. As a result, a differentiated cell develops specific structures and performs certain functions. In lab, stem cell can be manipulated to become specialised -> aka directed differentiation.
External signals:
chemicals secreted by other cells,
physical contact with neighbouring cells, and
certain molecules in the *microenvironment.

STEM CELL POTENCY
refers to the range of cell types to which a stem cell can give rise to.
It is determined by the number of possible pathways that it can take in its subsequent development, through the process of specialization/differentiation.
It reflects the differential potential of the stem cell.
3 basic measures of stem cell potency: totipotency, pluripotent and multipotency
The restriction on the potency of stem cells is gradual, and the potencies of these cells are determined by their surroundings. Once committed, however, they usually do not switch commitment. When placed in a new environment, they will not change the type of cells they generate.

Question 4

Adult stem cells

Answer 4

undifferentiated cell found among differentiated cells in a tissue or organ, can renew itself, and can differentiate to yield the major specialized cell types of the tissue or organ
rare. dispersed in tissues throughout the mature animal and behave very differently, depending on their local environment. There are many different types of stem cell, each restricted in the types of specialized cell it can give rise to; for example, there are blood, neural, liver and skin stem cells.
stem cell numbers in the body are very low making these cells extremely difficult to identify and purify. In addition, many stem cell types do not grow well in cultures where they also often lose their distinctive cellular properties.
Roles:
maintain and repair the tissue in which they are found, and
replace cells that die because of injury or disease.
Origin is unknown
small number of adult stem cells in each tissue
Defining properties:
can make identical copies of themselves for long periods of time via proliferation (long-term self-renewal).
They are able to give rise to fully differentiated cells that have mature phenotypes, are fully integrated into the tissue, and are capable of specialised functions appropriate for the tissue.
They are clonogenic i.e. a single adult stem cell can give rise to a colony of genetically identical cells, which then gives rise to all the appropriate, differentiated cell types of the tissue in which it
resides.
Identification of adult stem cells is based on two characteristics:
(a) appropriate cell morphology; and
(b) demonstration that resulting differentiated cell types display surface markers that identify them as belonging to a particular tissue.

Question 5

describe 2 unique features of stem cells that could be seen in the figure [2]

Answer 5

1. stem cells undergo differentiation to give rise to specialised cell types
2. stem cells are capable of dividing and long-term self renewal by mitosis
3. can remain undifferentiated for long periods of time

Question 6

describe the developmental potential of the one-celled zygote and the inner cell mass of the blastocyst [4]

Answer 6

one-celled zygote (any 2):
1. a totipotent stem cell
2. can form extra-embryonic membranes and the embryo
3. has the largest possible number of developmental pathways

inner cell mass of blastocyst:
1. pluripotent stem cells
2. they have the ability to give rise to cell types that form the 3 germ layers – ectoderm, mesoderm, endoderm
3. they do not have the development potential to make differentiated cells that form the extra-embryonic membranes

Question 7

multipotent stem cells can form unspecialised cell types of the tissue in which they reside. give an example of a multipoint stem cell and the specialised cell types that it can form. [2]

Answer 7

1a. blood stem cells
1b. can give rise to red blood cells and white blood cells
OR
2a. bone marrow stromal stem cells
2b. can give rise to bone cells/ osteocytes, cartilage cells/ chondrocytes, fat cells/ adipocytes and other kinds of connective tissue cells such as those in tendons

Question 8

what are the primary roles of these adult stem cells and describe one appropriate unique feature of this type of stem cells not mentioned in (a) [3]

Answer 8

primary roles:
1. adult stem cells maintain and repair the specific tissues in which they reside
2. they replace cells that die because of injury or disease
3. they can remain undifferentiated/ unspecialised for long periods of time

Question 9

suggest and explain why all the cells were removed from the donor trachea [3]

Answer 9

1. the need to avoid stimulation of an immune response that would lead to rejections of donor trachea/ foreign cells
2. any rejection would require continued care of the patient/ the need for taking immunosuppressive drugs in the long term
3. donor cells may be infected by viruses/ bacteria which may infect the host

Question 10

suggest and explain why the stem cells needed to be treated with chemicals to stimulate proliferation [3]

Answer 10

1. these chemicals act as ligands
2. to stimulate mitosis/ continue undergoing self-renewal
3. thus increasing cell number so there is enough cells to form the trachea

Question 11

suggest how stem cells can continue to divide mitotically whilst other cells can only do this for a set number of divisions [3]

Answer 11

1. stem cells possess telomerase while the other cells do not have telomerase
2. telomerase adds repeats to the telomeres, elongating and thus maintaining length of telomeres of chromosomes
3. stem cells can overcome Hayflick limit, leading to continued mitosis

Question 12

Adult stem cells such as these are described as multipotent.
Explain what is meant by the term multipotent. [1]
And
Suggest how it is possible that adult stem cells could differentiate into the range of cell types
needed for repairing retina. [2]

Answer 12

(e) Multipotent cells can differentiate into a limited number of cell types (but not into whole
organism) ;

1. each stem cell contains a complete genome ;
   cells will be in slightly different conditions / differentiate under appropriate conditions ;
   OR
2. through selective changes in genetic activity / different genes will be expressed, in
   different conditions ;

Question 13

State the level of potency of MSCs and describe its unique properties. [3]

Answer 13

1 *MSCs are multipotent;
any two :
2 It is capable of long-term self-renewal through mitosis ;
3 It is able to remain unspecialised ;
4 It can undergo differentiation / to give rise to specialised cell types, (quote at least
two from Fig. 3.5 e.g. myocyte / adipocyte / osteoblast / neuron / chrondrocyte) ;
5 It is clonogenic ;
*MP1 is compulsory for full credit

Question 14

Describe what human induced pluripotent stem cells (iPSCs) are and how they will help
overcome one such controversy. [2]

Answer 14

1 ref. to reprogramming (somatic) cells to synthesise pluripotent stem cells ;
A: adult stem cells
2 Thus there is no need for harvesting from embryos/ consent can be obtained from
donor/ ability to conduct stem cell research without use of stem cells ;
A: no destruction of human life / no disrespect for human life (in context of ESC)

Question 15

Compare the normal functions of totipotent, pluripotent and multipotent human stem cells. [13]

Answer 15

Similarities among totipotent, pluripotent and multipotent human stem cells:
1. They are unspecialised ;
2. 3. 4. 5. 6. 7. 8. They are capable of long-term self renewal via mitosis ;
They can give rise to specialised cells ;
They are capable of differentiating into more than one cell lineages ;
They express telomerase gene to produce telomerase to maintain length of telomeres ;
They respond to signal molecules to differentiate into specialised cells ;
They are clonogenic, a single stem cell can give rise to a colony of genetically identical cells ;
AVP ; (e.g. they are responsible for growth and repair)
Differences
[13]
D1 D1 D1 D2 D2 Totipotent stem cells can give rise to any cell type in the adult body AND any cell of the extra-
embryonic membranes ;
While pluripotent stem cells give rise to any cell type in the adult body that develop from the three
germ layers, excluding the extra-embryonic membranes ;
And multipotent stem cells can give rise to a limited number of specific cell types in the adult body ;
Totipotent stem cells are zygotic stem cells that are in the zygote / early embryo ;
While pluripotent stem cells are embryonic stem cells that are in the inner cell mass of the
blastocyst ;
D2 And multipotent stem cells are adult stem cells that are found in the organs and tissues ;
OR
D2 Totipotent stem cells consist of zygotic stem cells while pluripotent stem cells consist of embryonic
stem cells and multipotent stem cells consist of adult stem cells ;
D3 Totipotent stem cells are present at the earliest stage of embryonic development (before Day 5) ;
While pluripotent stem cells present at the blastocyst stage (after Day 5) ;
And multipotent stem cells are present throughout adulthood ;
D3 D3 OR
D3 Totipotent and pluripotent stem cells function from the point of fertilization to early development of
embryo while multipotent stem cells function throughout the individual’s life ;
D4 Totipotent stem cells and pluripotent stem cells are mainly for growth of the embryo while multipotent
stem cells are for growth, maintenance and repair of worn out tissues ;

Question 16

The use of stem cells for research and medical applications has potential benefits and risks.
Discuss why and how societies should regulate this technology. [12]

Answer 16

Why societies should regulate this technology [max 8]
A. Ethical and moral considerations
[12]
1. ref. to obtaining ESC from inner cell mass of blastocyst destroys its potential to develop into a human
being ;
2. 3. ref. to subjectivity in human rights of embryo / who gets to determine the value of an embryo’s life ;
if stem cell therapies become routine treatments, the spare embryos may be exploited as a source of
therapeutic materials, decrease respect for human life, ref. to respect for person ;
4. ref. to scientists being morally obligated to carry out stem cell research using ESCs to develop
treatments that alleviate human suffering ;
B. Potential benefits
5. 6. ability to create ESC by somatic nuclear transfer (SCNT) to produce cells for therapy ;
able to be created from the cells of patients suffering from rare, complex diseases, creating a vast
resource available for researchers ;
7. ref. to excess embryos not used for fertility treatments will be destroyed anyway, so should use
for medical/research purposes instead of wasting them ;
8. ref. to potential to lessen the demand for organ donors since ESCs can be used to grow organs for
transplant ;
9. AVP ;
C. Potential risks
10. beginning of slippery slope, dehumanising scenarios for embryo farms, cloned babies and fetuses used
for spare parts ;
11. encourage society to tolerate the loss of life to save a life ;
12. usage of SCNT may lead to misguided individuals to implant a cloned human embryo in a woman’s
uterus to create a cloned person ;
13. increase usage of ESCs might result in exploitation of women to donate their eggs ;
14. ref. to medical risk of tissue rejection during transplant of cells derived from donor ESCs ;
15. ref. to conflict of interest between fertility clinics and research/medical institutes for the use of high-
quality embryos ;
16. ref. oocyte retrieval is a highly invasive procedure, medical risk to donors ;
17. ref. to difficulty in gauging/verifying whether informed consent has been given ;
18. therapeutic/medical applications may only be available to those who can afford, ref. to justice ;
19. AVP ;
How societies should regulate this technology [max 8]
20. ref. to use of induced pluripotent stem cells (iPSCs) instead of ESCs for medical and research
applications ;
21. idea of using patient’s own cells to obtain iPSCs (which are differentiated into specialised cells) will
prevent tissue rejection ;
22. ref. to consent almost certainly given by patient, hence little ethical consideration needed ;
23. ref. to use of iPSCs avoids ethical issues such as viewing ESCs as potential life ;
24. ref. to regulation of accessibility of iPSCs (and ESCs) based therapy ;
25. require well-developed healthcare system with infrastructure for producing and distributing the iPSCs,
and trained specialists to manage and deliver treatments ;
26. require legal specialists to work with medical and research professionals to draw up laws and
regulations ;
27. ref. to establishing bioethics council (consists of specialists from different areas) to advise on
legislation ;
28. ref. to informed consent (for e.g., excess zygotes for IVF, oocyte donors, aborted fetuses)
29. ref. to education, creating public awareness ;

Question 17

Explain why GMP cells, which are progenitor cells, cannot be described as haematopoietic stem cells (HSCs) [3]

Answer 17

1. Differentiation has alr started (what I’ve missed out)
2. No self-renewal
3. Cannot form, all blood cell types

Question 18

Explain the unique features of stem cells and the normal functions of stem cells in a
living organism. [8]

Answer 18

Unique features
1. Stem cells are unspecialized, capable of dividing by mitosis and renewing themselves for
long periods and can differentiate to give rise to specialized cell types;
a. Unspecialised/undifferentiated cells with no tissue specific structures/do not carry
out any specific function;
b. Can undergo mitosis/divide indefinitely and undergo self-renewal to renew pool of
stem cells;
c. They have the ability to differentiate to produce specialized cells upon receiving
appropriate molecular signals;

2. Zygotic stem cells are totipotent. These cells can differentiate into any cell types to form
   whole organisms, and so are also pluripotent and multipotent;
3. Embryonic stem cells are pluripotent. These cells can differentiate into almost any cell
   type to form any organ or type of cell and so are not totipotent but are multipotent;
4. Blood stem cells are multipotent. These cells can differentiate into a limited range of cell
   type and so are not pluripotent or totipotent
   Normal functions
5. Embryonic stem cells are derived from the inner cell mass of blastocysts;
6. Pluripotent - able to give rise to almost all cell types;
7. To give rise three primary germ layers; ectoderm, endoderm and mesoderm / to the
   multiple specialised cell types / tissues / organs in the developing foetus;
8. Blood stem cells are found in the bone marrow;
9. Multipotent - able to give rise to different types of blood cells e.g. red blood cells, white
   blood cells and platelets;
10. maintain the steady state functioning of a cell by generating replacements ® repair for
    cells lost through disease, tissue injury or normal wear-and-tear;

Question 19

[2011 RI Prelim] Explain the differences between stem cells and cancer cells. [3]

Answer 19

a. Unlike stem cells, cancer cells do not differentiate and are unresponsive to molecular signals;
b. Cancer cells divide indefinitely while stem cell division is determined by molecular signals
[that either stimulates cell division or stop it altogether];
c. Cancer cells experience no contact inhibition and is invasive while stem cells experience
contact inhibition;
d. Cancer cells metastasize (dislodge from original tumour and form secondary tumours) while
stem cells remain in tissue of origin;

Question 20

[N2013/P3/Q5] Describe the features of blood stem cells and explain their normal
functions. [8]

Answer 20

1. type of adult stem cell;
2. found in bone marrow of long bones;
3. capable of dividing and renewing themselves for long periods;
4. unspecialized, does not have tissue specific structures for them to perform specialized
   functions;
5. can give rise to specialized cell types;
6. multipotent, can differentiate into a limited range of cell type, usually of a closely related
   family of cells;
7. e.g. red blood cells, white blood cells, platelets;
8. primary function is to maintain the steady state of functioning of a cell by generating
   replacement for cells lost through disease, tissue injury or normal wear-and-tear;

Question 21

Compare the normal functions of totipotent, pluripotent and multipotent human stem
cells. [13]

Answer 21

Similarities:
1. Stem cells are a group of undifferentiated* and unspecialized* cells;
2. They have the ability to differentiate* into specialized cells when appropriate molecular
signals are present;
3. Stem cells are capable of self renewal* to ensure a constant pool of stem cells with the
same development potential;
4. Stem cells divide by mitosis* to produce genetically identical daughter cells ;

Differences:
Point of
comparison

Totipotent
stem cells

Pluripotent stem
cells

Multipotent stem
cells

Examples 1a. Zygotic
stem cells* are
totipotent;

1b. Embryonic
stem cells* are
pluripotent;

1c. Blood stem
cells (myeloid
and lymphoid
stem cells)* are
multipotent;

Differentiation
potential

2a. They have
ability to
differentiate*
into all cell
types that
make up an
organism
including

extra-
embryonic

tissue* such as
placenta*,
which
nourishes
embryo;

2b. They have
ability to
differentiate* into
all cell types that
make up an
organism except
extraembryonic
tissue* such as
placenta*;

2c. They are adult
stem cells which
have the ability to
differentiate* into
limited range of
related cell types
- all type of blood
cells - but far fewer
types than the
pluripotent
embryonic stem
cell;

Functions 3a. They are
able to form
entire
organism;

3b. They cannot
form entire
organism as
extraembryonic
tissues such as
placenta is required
for foetal
nourishment and
development;

3b. They also
cannot form
entire organism
but they replace
cells that are lost
due to wear and
tear, or cell death
and injury, e.g.
myeloid stem cells
differentiate to
form red blood
cells and
macrophages,
while lymphoid stem cells
differentiate to
form B lymphocyte
and T lymphocyte

Examples and
sources

4a. They are
derived from a
fertilised egg
which forms the
zygote. Cells
that are
produced
within first 3
division (8 cell
stage*) after
egg is fertilized;

4b. They are
derived from cells
of inner cell mass
of blastocyst* at
about 4 to 5 days
post fertilization;

4c. Blood/
haematopoietic
stem cells, such
as myeloid and
lymphoid stem
cells are found
primarily in bone
marrow;

Question 22

Discuss why and how societies should regulate this technology. [12]

Answer 22

(A) Why societies should regulate this technology
Benefits of using embryonic stem cells
1. Embryonic stem cells are pluripotent* and have the potential to treat a wide range of
diseases as they have the potential to grow indefinitely in a laboratory environment and
can differentiate into almost all types of bodily tissue.
2. Treatments using ES cells could potentially be developed due to their ability to repair
extensive tissue damage and develop organs to replace those lost in injury or disease.
E.g. Treatments for physical trauma, degenerative conditions (e.g. Parkinson’s disease),
and genetic diseases (in combination with gene therapy).
Risks of using embryonic stem cells
3. Possibility of unforeseen consequences in treated patients such as possible risks of
tumor formation, immunological reactions, unexpected behavior of the cells, and
unknown long-term health effects.
Considerations of ethical problems
4. Some people assert that the embryo has the status of a human being as it has the
potential to become one. They believe that embryonic stem cell research violates the
sanctity of life and is tantamount to murder.
5. Some people object to extracting stem cells from an embryo to make replacement
body cells by treating the embryo as just a source of spare parts. Embryonic stem cell
research takes a purely utilitarian view of the embryo.
6. Justice and equity:
- Adult stem cell treatment is established and there are fewer ethical issues involved.
Thus adult stem cell research may be able to make greater advances if more money and
resources were channeled into it instead of embryonic stem cell research.
- As embryonic stem cell research is expensive, funds can be channeled to treat other
more treatable diseases.
7. Claims of the benefits of embryonic stem cell research are over-rated / few (if any)
examples of success in medical applications.
8. Current benign applications may lead to abuse in the future. Once human status is
denied to embryos, this precedent may extend to other categories of human beings such
as the profoundly disabled or the elderly infirm.
(B) How societies should regulate this technology
9. Enforce legislation on the period when ES cells can be extracted.
E.g.: Current UK legislation does not allow use of embryos that are more than 14 days
old. In fact, ES cells are obtained earlier from blastocyst (between 3-8 days after
fertilisation).
10. Researchers to consider using alternative techniques such as adult stem cells, from
sources such as umbilical cord blood, have already produced some results.
11. Institutionalise protocols for donation and consent - For those people involved in
donating eggs, embryos or tissues, ensure protocols allowing for informed consent,
understanding of research aims and privacy.
12. Offer induced pluripotent stem cells (iPSCs) as alternative source of stem cells
proposed for therapy and research.
Governmental research fundings to support use of iPSCs offers several
advantages:
12a. Since iPSCs can be derived directly from adult tissues, it does not generate or
destroy any human embryos;
12b. iPSCs can be easily procured from any type of adult/specialised somatic cell (e.g.
skin cell) without risk to the donor;
12c. In contrast to ES cells extracted from human embryos, iPSCs derived from a
patient’s own cells would open the possibility of generating lots of patient-specific cells,
which will not be rejected by the immune system upon transplantation;
12d. Further, it also allows the generation of pluripotent stem cell lines from patients with
inherited diseases, in order to better understand why the diseases develop and use in
personalised drug discovery efforts;
12e. An additional reproductive technology that may be enabled by iPSCs is the
generation of sex cells (sperm and eggs) for treating infertility;

Question 23

Explain how the introduction of mRNA into the cytoplasm of adult cells can result in the
production of iPSCs and why these iPSCs are footprint free. [4]

Answer 23

How introduction of synthetic mRNAs can produce iPSCs:
1. Translation* of the synthetic mRNAs will produce proteins which are needed to
2. switch off certain genes in specialised adult cells allowing them to de-differentiate;
3. and switch on expression of certain specific stem cell genes allowing the adult
somatic cells to achieve pluripotency;
Why are these iPSCs footprint-free:
4. The synthetic mRNAs do not enter the nucleus and will not intergrate with the
genomic DNA – they do not modify the genome of the adult cells;
5. The synthetic mRNAs are degraded after a while and will not have a trace inside the
cells;

Question 24

Explain how monozygotic twins develop from a single zygote to become

individuals that have DNA that is 100% the same. [4]

Answer 24

1. Undifferentiated* zygotic stem cells formed from fertilization of gametes
2. Are capable of undergoing extensive proliferation* via mitosis and self-
   renewal* 3. During interphase, Semi-conservative DNA replication* occurs to produce

daughter DNA molecules that are genetically identical.
4. During anaphase* of mitosis, genetically identical sister chromatids are
separate equally into opposite poles forming genetically identical daughter
cells.
5. Zygote and cells up to the 8-cell embryo remains totipotent* and can

differentiate* into all cell types that make up an organism including extra-
embryonic tissue* such as placenta*, and hence are able to form entire

organism;
6. This is a result of differential switching on of genes which occurs when
appropriate molecular signals are received;

Question 25

Describe the features and functions of myeloid stem cells. [3]

Answer 25

1. Myeloid stem cells are undifferentiated* and unspecialized* cells which are multipotent*; 2. They have ability to do self-renewal* and proliferate and to differentiate* into specialised cells; 3. They are able to do self renewal to ensure a constant pool of stem cells; 4. for growth and development; 5. Their ability to differentiate into specialised cells helps to regenerate/replace cells that are lost due cell death and injury;

Question 26

Epithelial stem cells and melanocyte stem cells are examples of a particular type of stem cell. State two key features of this type of stem cell. [2]

Answer 26

1. They are multipotent* stem cells that can differentiate into a limited range of specialized cell types in the presence of the correct molecular signals; 2. They are able to undergo extensive proliferation and self-renewal by mitosis* in the presence of the correct molecular signals and hence give rise to a constant pool of cells;

Question 27

Discuss how the presence of stem cells within the skin and the presence of hairs covering the skin influence the harmful effects of high levels of ultraviolet light on the health of mammals. [4]

Answer 27

1. The presence of hairs covering the skin play a protective role as they reduce exposure of the skin by blocking the harmful ultraviolet radiation; 2. Since stem cells are near the skin surface, the high levels of ultra violet light can damage the DNA is stem cells as; 3. the ionizing radiation can cause the DNA is the stem cells in the skin to mutate and if these mutations are in genes that regulate cell cycle checkpoints/proto oncogenes/ tumour suppressor genes; 4. it could lead to uncontrolled cell division/ tumour formation and increase the chances of an individual getting cancer; 5. especially because stem cells already have telomerase activity;