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THE USES OF

EMBRYONIC STEM CELLS


existing body cells however [2]. Thus a significant
amount of stem cells can be obtained, meaning
researchers have the ability to treat almost all diseases
which could potentially lead to the regrowth of organs
or limbs.

1. ABSTRACT
This research paper explores the very
controversial concept of the various medical uses of
embryonic stem cells and the limitations we face as
humans. There are many ethical issues with the use of
these stem cells, however they are still used due to
their ability to revolutionise modern medicine. This
paper looks at the advances over the recent years and
how new developments could potentially devise
treatments to limit the effect of diseases such as
diabetes, heart disease and Parkinsons [1]. The main
priority is to analyse recent research and discuss what
this could mean for future developments and
treatments for common diseases.
The current use of embryonic stem cells is
very advantageous as vital research is in place to find
new cures for diseases such as Parkinsons that may
not be able to be cured without these cells. Despite
this, from my research I can conclude scientists will
avoid using embryonic stem cells in the future as soon
as more research has been carried out into adult stem
cells, in order to avoid the many ethical and moral
issues that embryonic stem cells pose.

2.1 Human embryonic stem cells


Human embryonic stem cells (hESCs) however are
derived only from eggs that have been fertilised to
produce embryos, cloned embryos or aborted foetuses.
These eggs are usually fertilised in an in vitro
fertilisation clinic - where the egg is removed from the
uterus and fertilised with the sperm in culture dishes. A
feeder layer is at the bottom consisting of skin cells
which are designed not to replicate any further and a
nutrients layer (culture medium) which provides a
surface for the cells to rest on.

2. INTRODUCTION
A stem cell is an unspecialised cell that has the
ability to reproduce using cell division. They are used
for repair within the body and thus have the potential
to develop into many different cell types in the body
during early growth. As a stem cell divides, the
daughter cells have the ability to become a new stem
cell or become another cell with a specialised function
such as a muscle cell for example. Typically a stem
cell will only divide when required for renewal of

Figure 1: This shows the process of stem cell cultivation


the process in which stem cells are produced from the egg
and the steps which are involved. (1)

This process creates the blastocysts before they are


implanted into the lining of the uterus. From here,
some blastocysts which are not implanted, with
consent from the donors, they can then be used for
research purposes. It is typical to generate 8 to 10
blastocysts using this process but a maximum of 2 will
be implanted. The others will be frozen for future use;
for example if the pregnancy was unsuccessful or they
would like another child. If they would not like to do
this however the blastocysts can be donated for
scientific research despite the great ethical debate
only the inner layer of cells are harvested for
laboratory use [3].

found in the bone marrow and some have since been


used in transplants.
The disadvantage of this type of cell is that they
are only found in some tissues and in very small
numbers which makes it more difficult for research
and development as they only divide when destroyed
or damaged.
These stem cells can be reprogrammed to act in an
embryonic stem cell like manor by expressing
important genes and factors shown by the embryonic
stem cells. However this wasnt discovered until late
2007 in humans so there is still a great deal of research
needed before they will reach their full potential.
Further research into reprogramming these stem cells
could lead to vital developments in the future as they
express similar properties to embryonic stem cells
without the ethical debate [4, 5].

The embryonic stem cell is a highly valued type of


stem cell as they are pluripotent which means that they
are capable of developing into many cell types. Before
this period however they are totipotent which means
they have the ability to divide creating a whole new
organism [4].

For the last 40 years adult stem cells have been


used in use in transplants in patients suffering from
diseases such as leukaemia and other blood related
diseases and have been used in bone marrow
transplants for many years. Overall, although these
stem cells are less controversial it is very difficult to
harvest them in large numbers which means that
practically it is very difficult to research them.

In 1981 it was discovered that they could be


derived from early mouse embryos, however it wasnt
until 1998, due to the work of Thompson, where stem
cells could be derived from human embryos. This was
the first step in the use of embryonic stem cells [2].
They are derived from blastocysts an embryo of only
150-200 cells that is not contained within the body, if
taken from a later stage than this the cells will have
already begun to differentiate, so they arent quite as
malleable and hence arent as useful for research.
Blastocysts are typically 3 to 4 days old, as at this
point they have not specialised and have the ability to
become any type of cell in the human adult body. Once
a cell has specialised it cant be directed to become a
different type of cell if it has specialised as a blood
cell it cant then become a skin cell [3].

2.3 The purpose of the research


Although a large part of stem cell research is
discovering how cells work, it is also about figuring
out how problems arise, either from birth or
developing problems such as disease. For example,
the stem cells can be differentiated to a specific cell
type which can then be used in drug testing to see how
they react or what effect a specific drug has on them.
This means that investigating and determining possible
treatments for many diseases is possible due to them
being pluripotent [6].

2.2 Adult stem cells


Although my research is directed at embryonic
stem cells, adult stem cells (also known as somatic
stem cells) are another type of stem cell; however they
are multipotent not pluripotent so there is a limited
number of cells that they can develop into. They are an
undifferentiated cell found within a tissue or organ,
surrounded by differentiated cells and their role is to
maintain the tissue in which they are found. These
cells were discovered in the 1950s when it was
realised that there were at least two types of stem cell

2.4 Potential uses


Cell based therapies would be an incredible
achievement for embryonic stem cells. Organ and
tissue transplants are a huge part of medicine today,
however in order for these transplants to take place
there has to be a donor. This is often a huge challenge
as the need for certain organs and tissues is greater
2

than the supply, thus directing stem cells to


differentiate into these specific cells will allow
replacement tissues and organs to be produced without
the strain of limited availability [7]. This development
would allow many diseases which are currently
incurable to be treated and potentially cured. For
example currently age-related macular degeneration is
being treated in London with the use of particular eye
cells which are produced by embryonic stem cells [6].

A heart attack is when one of the coronary


arteries comes completely blocked, usually from a split
plaque, which triggers a clot preventing the transport
of blood to the heart. The heart muscles and tissues
become starved of oxygen and begin to die, without
medical intervention the cells will continue to die until
the heart is unable to function completely. Once a heart
attack occurs the artery needs to be unblocked to
restore flow either via surgery or drugs. The area
affected will be smaller the sooner action is taken [9].

This could lead to treatment for other diseases such as


arthritis, heart disease, stroke, diabetes and spinal cord
damage.
3.1.1 Research into Heart Disease
2.5 Summary

Over the years large amounts of research has


been carried out into the possibility of regenerating
heart tissue by the use of stem cells. There have been
various treatments for many years helping patients to
manage the disease with daily medication, however
there is no cure as of yet. Stem cells may be able to
solve this issue as it has been discovered that
embryonic stem cells can be manipulated to produce
new heart cells - known as cardiomyocytes. However
these heart cells are young and so resemble the heart
cells of a young child and not the mature cells which
you would find in an adult. If these cells were
transplanted they would not be able to survive and
function correctly as they are not adapted for that
environment. Also only a small number of cells
manipulated develop into the heart cells required so it
is a very lengthy process to obtain large enough
numbers for transplant [10].

Embryonic stem cells are used greatly for research


purposes however they are not used currently used in
transplants and it is unlikely that they ever will be due
to ethical and legal issues, however induced
pluripotent stem cells made from adult tissues largely
remove concerns people have from deriving cells
directly from embryos so these have the potential to be
used within transplants.

3. DISCUSSION
3.1 Heart disease
Coronary heart disease is a worldwide problem
which takes the lives of more than 73,000 people in the
UK every year. Although treatable, 1 in 6 men and 1
in 10 women will lose their lives to the disease. There
are many symptoms which are associated with heart
disease such as heart attacks, heart failure and angina
(severe chest pain); however these are not experienced
by everyone [8].

The technology to produce heart cells from


both embryonic and induced pluripotent stem cells is
well developed, however only a very small number
which are derived have the potential to mature into
normal adult heat tissues. Induced pluripotent stem
cells have a major advantage over embryonic stem
cells as cells from the recipients own skin can be used,
this means it may be possible to produce cells that are
exactly identical to the recipients and so there is no
chance of rejection. Also these cells do not have the
same ethical issues experienced by that of embryonic
stem cells. Currently research is being conducted to
observe the developmental stages of these cells in the
hope of being able to program the cells to develop to a
mature state.

The disease is caused when there is a reduced


supply of blood to the heart caused by a restriction of
the blood carrying capacity of the coronary arteries
leading into the heart. This restriction is caused by a
build-up of fatty deposits. Gradually the lining
becomes thickened with sludge like substances formed
from cholesterol, these substances are called plaques.
This process is known as atherosclerosis and can lead
to high blood pressure and an increased risk of heart
attacks.

The intricate structure of the heart plays a very


important role in these developments, immature cells
3

are being implanted into the adult heart and the hearts
matrix is then manipulated to guide the development of
the immature cells. By observing the hearts scaffold
material through the development of the immature
cells scientists can observe the specific chemicals
which are required throughout the process. Therefore
they can then replicate these chemicals in a laboratory
type environment to construct fully developed adult
heart tissue by the use of embryonic or induced
pluripotent stem cells entirely [10,11].

Dementia describes various disorders of the brain


showing symptoms such as memory loss, thinking
difficulties, problem-solving or language [12].
Alzheimers however is a disease which causes
damage to the brain tissue and was discovered first in
1906 by Dr Alois Alzheimer who studied the brain
tissue of a woman who had died of a suspected
unknown mental illness. The changes observed to the
brain tissue are now known to be the characteristics
shown by the disease. This involves the brain slowly
atrophying (wasting away) in particular areas such as
the cerebal cortex. It is a rare disease to be found in
younger people and the risks increase with age. Other
factors include major head traumas and injuries as well
as family history.
People suffering with Alzheimers will
experience various symptoms but over time these
symptoms will progress. A major symptom is short
term memory loss, patients may have the ability to
remember events from months and even years ago but
forget things that have only just happened. This is
because there are several processes involved in
remembering an event, it is first retained for a brief
while in a short-term memory store before being
moved either to the long-term memory where it can be
recalled or forgotten completely. People with
Alzheimers lose the ability to add additional
information to their memory store and recall any
existing memories [14]. Despite this, eventually
patients may develop behavioural and communication
problems and could need 24-hour care. Despite the
mental degeneration people can live for many years
with the disease and it is not usually the eventual cause
of death [13].

Figure 2: Showing how the heart cells are acquired and


combined with the stem cells in order to assist further
research and testing. (2)

As with any stem cell transplant, tumours are a


huge issue. Before the transplant takes place it has to
be ensured that the specialised cells are separated from
the pluripotent cells as if this does not occur then the
unspecialised pluripotent cells will continue to divide
forming a tumour. This is achieved by observing the
code of proteins on the surface of the cell. The same
types of cells will have the same code of proteins so
outliers can be effectively identified and removed [10].

Alzheimers is formed due to the loss of


synapses, meaning the neurons cannot transmit the
signals to the target cell this could be a brain cell or a
motor neurone etc. This loss of connection between
cells eventually causes them to die resulting in loss of
use in parts of the brain.

3.2 Alzheimers Disease


Alzheimers is the most common type of
dementia found today; approximately 60 % of all
dementia cases are accounted for by Alzheimers [13].
4

3.2.1 Research into Alzheimers disease

disease by using stem cells to mimic the features of the


disease. By using pluripotent stem cells it has been
observed that certain changes in the presenilin 1 gene
is responsible for early onset Alzheimers.
Furthermore, past research highlighted that certain
neurons are responsible for the disease; these neurons
have since been analysed and it has been discovered
that the distribution of specific products contained
within the neurons could be a possible cause of the
Alzheimers disease. This research was a major
breakthrough as it allowed researchers to see what
needed to be done next. In order to progress with
research and treatment stem cells need to be
programmed to develop into both normal neurons and
neurons displaying the features of Alzheimers disease;
these can then be used in drug-testing and development
[17].

Figure 3: This image shows the effect Alzheimers has on


the brain. On the left is part of a healthy brain and on the
right is a brain of a sufferer of the Alzheimers disease. This
side is clearly much smaller and has dark regions showing
severe shrinking. (3)

3.3 Macular Degeneration


Macular degeneration is an age related disease
which is nearing treatment with the use of human
embryonic stem cells. Despite this the chances of you
developing the disease increase if you are female,
smoke, are exposed to high levels of sunlight or do not
have enough vitamins in your diet. The disease itself
affects a small part of the retina called the macula
which is responsible for seeing colour and detail,
macular degeneration therefore causes problems with
central vision. The disease makes things appear
distorted or blurry if youre looking at something
directly and can eventually lead to a blank patch in the
centre of your vision.

Alzheimers is caused when parts of the brain


waste away which alters the brain structure and
therefore its function. Usually this is alongside with
abnormal amounts of fibres, protein and acetylcholine
which prevent neurons functioning correctly and
gradually destroying them. The usual parts of the brain
which are affected are the grey matter (area
responsible for processing thoughts) and the
hippocampus (area controlling memory) [15].

Symptoms of the disease include difficulty


reading small text as well as straight lines beginning to
look wavy and distorted.

There are a few features found in many


Alzheimers cases, these are:

The macula itself is no bigger than pinhead


and contains a few million cone cells (a specialised
type of photoreceptor cell) which are sensitive to light.
They are most effective in areas of bright light to allow
you to see fine details, however when macular
degeneration develops these cells become damaged
and are prevented from working as they should [18].

Amyloid plaques which small composed


pieces found deposited between the nerve cells
in the brain
Neurofibrillary tangles which is when tau (a
normally useful protein) clumps together and
interferes with the neurons possibly to the
extent where they die as a consequence.
Shrinking of brain tissue which occurs when
the neurons die [16]

Current research is directed at focusing on the


genetic changes that lead to hereditary Alzheimers
5

using cells derived from human embryonic stem cells


in the UK. However Professor Coffey has also been
working towards deriving the cells from the patients
themselves. The main advantage of this treatment is
that the cells will be individual and specialised to the
patient so will provide a near perfect match with little
chance of rejection which could occur with the
embryonic stem cell approach.
In order to reach this discovery a great deal of
research took place, the trials began in 2007 where it
was proved that by replacing the damaged RPE cells
under the macula with healthy cells from a different
area vision could be restored. However this meant
complex surgery as healthy cells were required and
had to be removed from another area on the eye or
possibly the other eye of the patient before then
replacing the old cells. This complex surgery was
impractical due to demand and recovery time was
increased [21].

Figure 4: Here is the structure of the eye. The macula is


clearly positioned at the rear of the eye on the retina. (4)

3.3.1 Dry AMD


This is a more common and less serious than
wet AMD, around 90% of all AMD cases are dry
AMD. This type of macular degeneration develops due
to a build-up of white or yellowish deposits called
drusen (waste products) on the retina beneath the
macula. This is a gradual disease so it takes many
years for loss of vision to occur.

With the use of human embryonic stem cells


and adult stem cells from particular individuals, trials
were carried out to reprogram the cells before then
being transplanted into an animal model of

3.3.2 Wet AMD

AMD for testing to demonstrate that visual


function can be significantly improved. It is vital that
these stem cells behave as normal RPE cells as well as
sharing the same gene profile as a natural human RPE
to avoid rejection.

Wet AMD is the less common type of AMD


only affecting 10% of AMD sufferers. This is a much
faster, more serious disease and vision can deteriorate
in a matter of days if not treated. It occurs due to blood
vessels forming beneath the macula; as these are
abnormal they tend to break or bleed which damages
the macula further causing it to pull away from the
base. This accounts for the rapid loss of central vision.

Despite the initial trials taking place in 2007, it


wasn't until till many years later when human trials
took place. Treatments to human patients suffering
with the disease by injecting the stem cells to the
damaged area have been made and a significant
improvement in vision has been seen by most,
however there are still a number of patients observing
no physical effect. There are no known complications
known due to the transplant itself, however the method
used to insert the stem cells has been known to cause
some complications. It has been known for the method
to induce cataracts, endophthalmitis and inflammation
of the eye; although not caused by the stem cells
themselves treatment is still being developed and
further trials and studies are taking place to reduce
procedural complications [22].

3.3.3 Research into Macular Degeneration


The disease will not necessarily develop the
same way or at the same rate in both eyes so it is
possible to experience wet AMD in one eye, while
suffering from dry AMD in the other. However people
suffering with dry AMD can later go on to develop the
more harmful wet AMD [19, 20]
AMD occurs when the retinal pigment
epithelium cells (RPE) within the eye become
damaged. These cells form a lining on the inside of the
eye under the retina and vision is greatly affected if
these cells become damaged. Professor Pete Coffey
has programmed human embryonic stem cells to
develop into the RPE cells which are needed for
treatment. This resulted in the first clinical trial of
6

3.4 Diabetes

3.4.2 Type 2

Diabetes is a condition causing a higher blood


sugar level than normal and affects more than 365
million people worldwide. There are many reasons
why this can occur, hence why there are so many
different types of the disease. As food is digested, it is
normally converted into sugar for use around the body
or stored as glucose. It is almost impossible to get
glucose into the cells naturally, so a hormone called
insulin is used to assist the glucose into the cells. The
insulin is created in the pancreas - an organ located
near the stomach. A sufferer of diabetes will make too
much insulin or will not be able to use the insulin that
it creates leading to a high build up of sugars within
the blood.

This type of diabetes is usually caused due to


being overweight or family history. As obesity is a
rapidly increasing problem, so is the problem of type 2
diabetes. Obesity has now become more serious than
cigarette smoking which is a major concern for health
today as there are many long-term complications
associated with the disease. These include
cardiovascular disease, acute coronary syndrome, heart
disease, stroke and many more life threatening
diseases. Another major issue of this type of diabetes it
cost, already consuming over 10% of the total
healthcare budget, a permanent solution needs to be
established [26].
3.4.3 Research into Diabetes

Many health issues can occur as a result of


diabetes such as kidney failure, heart disease and even
blindness. However there are many different types of
diabetes with various causes, symptoms and
treatments, the most common types being type 1 and
type 2 [23].

Sufferers of diabetes often requires artificial


insulin injections or other insulin based medications,
therefore initial research was targeted at producing
artificial insulin in a laboratory with the use of stem
cells. Human embryonic stem cells are pluripotent,
thus they are ideal as they can be programmed to
produce any type of cell. In 2004 the genes 'cdk' and
'cyclin d' were introduced with the use of a virus in
order to produce beta cells which produce the insulin
required by sufferers of the disease [27].

There is another increasingly common type of


diabetes called gestational diabetes which occurs in a
small number of pregnant women however this tends
to disappear following the birth so it is not a lifelong
health issue and it can normally be controlled with diet
and exercise alone so does not require the use of
medication [24].

In order to cure a patient with diabetes the


insulin producing cells of the pancreas that have been
damaged or destroyed have to be replaced with
functioning, viable cells. Currently there is not a cure
for diabetes sufferers, whole pancreatic transplants are
viable and accepted however this is a very time
consuming process and the demand is much greater
than the supply, therefore this is not a permanent
solution. Islet cell transplants have also been
attempted; this is a process whereby the cells of the
pancreas that secrete insulin are injected directly into a
sufferers pancreas [28].

3.4.1 Type 1
Type 1 diabetes is where the pancreas does not
produce any insulin at all; this means that insulin has
to be injected into the blood. This is the most common
type of childhood diabetes and has normally developed
by the age of 40, however it only accounts for 10% of
all diabetes cases. As the pancreas is not producing any
insulin the glucose cannot be moved out of the blood
and used for energy like it normally would. This
causes the body to begin to break down its own fat and
causes severe weight loss and dehydration if not
treated. This type of diabetes is known as a
autoimmune condition, this is where the cells in your
pancreas are seen as harmful causing the immune
system to automatically react and destroy the cells by
mistake [25].

In 1998 researchers discovered a method of


isolating and growing human embryonic stem cells,
and it was since this development that the possible
treatment of diabetes has been developed. This
method involves cultivating stem cells into the insulinproducing islet cells which are found in the pancreas,
the benefit of using these cells is that there is less
chance of rejection than some alternative techniques
that have previously been used and also they can be
genetically programmed to be slightly different to the
7

normal beta cells found within the pancreas in the


attempt to avoid detection from the immune system.
The current issue with this approach is that it does not
provide a replenishing supply of insulin so would not
provide a permanent treatment for the disease, further
intervention and treatment would also be needed [29,
30].

treatments for animals have also been researched that


could be used within veterinary medicine.
There is a huge benefit to the use of stem cell
technologies, organ repair or organ regeneration could
become possible which reduces the demand for human
donors for transplants. A greater understanding of
current diseases can be gained, allowing a deeper
knowledge into their background as well as finding
potential treatments to decrease and even eradicate
certain currently incurable diseases.

Ultimately type 1 diabetes may be very


difficult to treat as the cells are destroyed when the
immune system attacks them, so even if new, healthy
cells were transplanted to replace the destroyed ones,
without some control on the immune system it would
also destroy the newly transplanted cells. However the
stem cells contain endothelial precursors, which not
only help treat the disease but also reduce the patients
chances of developing kidney disease. Thus the
autoimmunity must be overcome before any transplant
will be viable.

However stem cell research relies greatly on


money and the use of animals for initial testing.
Therefore as well as being deemed as unethical, the
use of animal testing is also seen as a problem as many
people are against the potential unnecessary harm of
animals. On the other hand however, without the use
of animals this testing could not take place which
makes it extremely difficult for researchers to predict
the effects these treatments will have on humans. In
order to avoid this, researchers may use slices of
human tissue to test stem cells as this means no animal
welfare issues and it is up to the individual if they wish
to participate or not.

4. CONCLUSION
Stem cells have drastically improved our
understanding of many diseases and have since
provided treatments to replace damaged tissues and
cells. Not only has stem cell research allowed
scientists to gain a greater insight into diseases, the
capability and complexity of human embryonic stem
cells themselves has also been explored. Due to
developing technology more aspects of stem cells can
be observed and tested, allowing new research to take
place.

Although other treatments do exist for some of the


diseases mentioned, they do not offer a permanent
cure, only reduce the symptoms or mask the disease all
together. Human embryonic stem cells are the only
type of cell that have the ability to differentiate into
any cell type, therefore making them suitable for wide
source of diseases and thus ideal to research.
Personally I think that with further research more
diseases will be able to be treated and methods may be
possible to reverse the effects of the diseases.
Although I think eventually the potential need for
human embryonic stem cells will outweigh the ethical
debate, this could take many years. The use of induced
pluripotent stem cells is also a potential for treatments
as these cells can be transplanted without the ethical
issues. Although there is more chance of rejection with
these cells and they are cannot develop into any cell
type like the embryonic cells there are still perfectly
viable treatments that can be achieved.

There are many potential future developments for


human embryonic stem cells, many trials have taken
place but, due to the extreme abundance of ethical
issues, they are not used in transplants currently.
Although treatments of diseases such as age-related
macular degeneration and Parkinsons disease are
nearing treatment, it is unclear if these will be treated
with the use of human embryonic stem cells or the less
controversial induced pluripotent stem cells. However
there are many more diseases undergoing further
research such as: heart disease, Alzheimers, stroke
and diabetes. The use of these stem cells could have a
large impact on many peoples lives and decrease the
development of certain diseases. But it is not only
humans that could benefit from this research,

In the future it may also become possible to


externally clone the stem cells, this would be a major
breakthrough in medicine as it removes the ethical
issues that stem cells pose.

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