The Role of Embryonic Stem Cells in Tomorrow’s Medicine with
Consideration to the Technical and Ethical Issues Surrounding
Them
BY
Claire Surgeoner
Abigail Curry
Pass
RESEARCH PAPER
BASED ON
PATHOLOGY LECTURES
AT MEDLINK 2011
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Abstract
Stem cells are the 'master cells' of the body from which all other cells, tissues, organs
and bone are created. The purpose of our paper is to explore the use of a certain type of
stem cell: the pluripotent, embryonic stem cell, which has been promised by many to
cure many conditions. Our idea was to explore the future implications and contributions
to medicine that the advancements that embryonic stem cell technology would make
and to consider the ethical issues concerned with this part of pioneering science. While
there are several technical issues to be overcome, such as specifying cell differentiation
and controlling dividing cells, and ethical issues, we believe that the potential embryonic
stem cells have in curing what are to date ‘incurable’ diseases, mean that it is a new era
in science that is unfathomable.
Introduction
A stem cell is found in any multicellular organism and can divide through mitosis and
differentiate into any type of body cell; when a stem cell divides, the new cell can
become a different cell with a more specific function, such as a heart, blood or
muscle cell, or it can remain a stem cell.
Nearly thirty years ago, in 1981, Scientists at the University of Cambridge discovered
ways to derive embryonic stem cells from mouse embryos. This detailed study led
other scientists to a new discovery in 1998 of a way to derive stem cells from human
embryos and grow the cells in the laboratory. These have since become known as
human ‘embryonic stem cells’. Through in-vitro fertilisation procedures, multiple
embryos were created for reproductive purposes. When they were no longer needed
for that purpose, they were donated to scientific research with the informed consent
of the embryonic stem cell donor. In 2006 there was another breakthrough when
scientists discovered specific conditions that would permit some specialised adult
cells to be reprogrammed to assume a stem cell – like state. These cells became
known as ‘induced pluripotent stem cells’.
Stem cells have the potential to enable scientists to create new organs, regrow
crippled body parts e.g. eyes, hearts, spines, or reverse the damage of chronic
illnesses such as diabetes, Alzheimer’s and Parkinson’s disease. For example,
Parkinson’s disease affects 120,000 people within the UK. It affects the way the
brain co-ordinates body movements such as walking, talking and writing. Imagine if
we could, using stem cells, cure 120,000 people in the UK and thousands more
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worldwide allowing them the freedom to live their lives as ‘normal’ by the end of the
21st Century.
Stem cells are fast becoming a major development in medical
technology and have the potential to cure many illnesses which as of yet are
‘incurable’. However, before stem cells can be used on a worldwide scale there are
several technical, political, and ethical obstacles to overcome.
Stem cells are capable of proliferation, unlike muscle, blood or nerve cells which
cannot generally replicate themselves. This is the unique property which allows stem
cells to potentially cure these illnesses. Scientists are trying to understand two
fundamental properties; how embryonic stem cells can proliferate indefinitely without
differentiating (differentiation is the process by which less specialised cells become
more specialised cell types), and how living organisms regulate dividing cells. The
answer to these issues would enable scientists to grow embryonic stem cells in the
laboratory more effectively and enable them to understand the signals within the
body that regulates cell division, thus enabling them to learn more about abnormal
mitosis which leads to cancer. As long as the embryonic stem cells in culture are
grown under the appropriate conditions, they can remain undifferentiated and
unspecialised. However, if cells are allowed to clump together to form ‘embroyoid
bodies’ they begin to differentiate spontaneously. If scientists can reliably direct the
differentiation of embryonic stem cells into specific cell types, they may be able to
use the resulting, differentiated cells to treat certain diseases in the future.
There are three main types of stem cells;

Embryonic Stem Cells

Adult Stem Cells

Induced Pluripotent Stem Cells
Embryonic stem cells, as their name suggests, are derived from embryos. Most
embryonic stem cells are derived from embryos that develop from eggs that have
been fertilised in an in-vitro fertilisation clinic , which have been donated for research
purposes with informed consent of the donors. They are not derived from eggs
fertilised in a woman's body. These stem cells come from embryos that are four to
five days old. At this stage, an embryo is called a ‘blastocyst’ and has about 150
cells. These are called ‘pluripotent’ stem cells, meaning they can divide into nearly all
cells,or they can specialise and become any type of body cell. Because of this
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versatility, embryonic stem cells have the highest potential for use to regenerate or
repair diseased tissue and organs in people. Figure 1 shows the differentiation of a
human embryonic stem cell.
Figure 1
Induced pluripotent stem cells (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 properties of embryonic
stem cells.
As well as the foetus where embryonic stem cells are found, other types of stem
cells may be located in the placenta, amniotic fluid and umbilical cord, and they
remain in many adult tissues. Cord blood is sometimes collected at birth today, and
the stem cells stored.
Adult stem cells have been found in: bone marrow, blood, the retina and cornea,
intestine, liver, muscles, nervous system and the brain, pancreas and skin. These
"pluripotent" stem cells are less flexible than embryonic stem cells and are typically
only able to form cells of the tissue in which they reside. "Adult" distinguishes these
cells from their embryonic equivalents, but they are present across all age groups,
not only ‘adults’. Unlike embryonic stem cells which can transform into any type of
cell, adult stem cells have a limited capacity to form into some types of cell.
As of mid 2010 hundreds of clinical trials involving stem cells have been registered
trialing the use of stem cell therapy in treating many different conditions. Currently,
there are thousands of trials testing the use of stem cells in Veterinary Applications,
as demonstrated by the work of Trounson (2007). Research performed with
domestic animals such as dogs and cats are benefiting the development of stem-cell
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treatments for human use. The aim of this research is that it may lead to
developments in treating strokes, tendon and ligament damage, osteoarthritis and
myocardial infarction, in animals and in humans. The high frequency of illnesses
within animals, such as racehorses and circus animals, has put veterinary medicine
at the forefront of this new regenerative approach. Companion animals are perfect
candidates for research about possible applications in medicine for humans, as
they’ve been shown to closely mimic the human condition and disease in clinical
trials.
An example of the pioneering research into stem cell therapy is research into treating
spinal cord injury and Lou Gehrig’s disease (as illustrated in the work of D. Kerr
2006.) The main target for the therapies have been animals with spinal cord injuries,
and the aim was to help them regain movement. Human embryonic stem cells were
used to make functional motor neurons which gave scientists insight into how they
might one day replace human motor cord neurons.
Research in human embryonic stem cells is a rapidly developing scientific field. In
this paper we will be considering the potential human embryonic stem cells have in
treating blindness and vision impairment, deafness and hearing loss, baldness and
diabetes.
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Discussion
The eye is a good place to test stem cell-derived treatments, because it is somewhat
self-contained and the immune system is less active there. This means that cells
transplanted into the eye are less likely to be attacked and destroyed by the
recipient’s immune system.
In another new clinical trial using stem cells, scientists injected human embryonic
stem cells – derived retinal pigmented epithelial cells (RPEs) into a patient’s eye who
was suffering with AMD (age-related macular degeneration.) AMD is the leading
cause of vision loss in humans over 60 years of age. It is caused by the leading loss
or damage to light-sensitive cells called ‘photoreceptors’ at the back of the eye, and
loss or damage to the supporting cells called retinal pigmented epithelium, that
nourish receptors. Startgard disease is an inherited form of macular degeneration
that shows up earlier in life, rather than during aging. As described in the work of
Schwartz in 2012, in one clinical trial, designed to test the safety of a proposed
therapy, scientists injected stem cell-derived RPEs into one eye of a patient with
AMD. In a second trial, scientists injected human stem cell-derived RPEs into the
eye of a different patient who had Stargardt disease. Both patients tolerated the
treatment well, with some eyesight improvement reported. Scientists hope to treat
these diseases by replacing the RPE cells and have developed a protocol to coax
human embryonic stem cells to differentiate into RPE cells. However, these are just
two cases and so for the treatment to gain broad acceptance, many more trials must
be conducted.
Deafness is a major problem in people: millions of people worldwide become deaf or
hearing impaired every year. This can occur if a person's inner-ear hair cells are
destroyed by exposure to loud noise, to some antibiotic drugs, or simply through old
age. The hair cells act like miniature microphones, capturing sound vibrations from
fluid in the ear and translating the movement into nerve signals. These cells are
found in the inner ear and do not grow back if damaged, which can result in
permanent hearing loss. An approach to re-growing the hair cells is to use embryonic
stem cells, with research in this area led by Stefan Heller and colleagues at the
Massachusetts Eye and Ear Infirmary in Boston, US. Heller's team produced the
inner-ear hair cells by exposing mouse embryonic cells in the lab to chemical factors
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which steer the natural development of hair cells. The team then implanted them into
chicken embryos and the cells continued to develop just like the native hair cells
already present in the chick embryo. After treatment, the researchers used sensory
electrodes around the animals' heads to show that the auditory nerves of treated but not untreated - animals were now registering sound. One future possibility would
be to use the therapy to improve hearing in people who already wear cochlear
implants. These electrical devices are of some help to people lacking hair cells, but
the re-growth of even some hairs could boost their hearing further. This laboratory
study developed a way of manipulating mouse embryonic stem cells to develop into
cells that were similar to sensory hair cells. The cells appeared to resemble sensory
hair cells in shape and their ability to respond to movement. Stem cells could not
only be used to replace the lost hair cells in the ear, but also any damaged nerve
cells along which the signals generated by the hair cells are transmitted to the brain.
Both Type I and II diabetes affects roughly 346 million people worldwide. Diabetes is
a long-term condition caused by excess glucose in the blood. In the UK alone
diabetes affects 2.8million people, with a further estimated one million people with
undiagnosed Type II diabetes. Stem cells have the potential to provide an unlimited
source of cells for research, replace missing or damaged insulin-producing cells,
replace other cells damaged by diabetes, or reboot the faulty immune system
responsible for causing Type I diabetes. Understanding the root causes of diabetes
has eluded researchers for many years now. The way in which the immune system
causes the destruction of precious beta islet cells within the pancreas of diabetics is
generally understood to be the key. To cure Type I diabetes, stem cell replacement
needs to be more than simply a case of swapping insulin-producing cells from a
healthy pancreas with those destroyed by diabetes in a diabetic patient. Pancreas
transplants are one form of procedure that has proven effective. However, the
demand far outweighs supply and the procedure is expensive. In Type I diabetes,
the body’s immune system becomes programmed to attack the beta cells, so the
patient must take a significant amount (some previous patients are require up to 18
tablets per day to prevent a total relapse) of immuno-suppressant drugs to prevent
this happening. To some people these drugs have caused them more time, money,
pain and annoyance than their diabetes ever did. Doctors and scientists have tried to
cure the disease through injections of pancreatic islet cells. Unfortunately, due to the
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need to suppress the immune system, only a small proportion of these therapies
have proved to be effective. Many patients have said that they have either had a
total relapse, or are at least still partially dependent on their insulin injections.
Scientists need to work out how to prevent the beta cells from being attacked by the
immune system For current treatment methods to be effective least are able to
produce one single accessible’ tablet’ which is effective at preventing the body’s
immune system from attacking the beta cells. Figure 2 shows the Hair cells located
in the cochlea of the inner ear.
Figure 2
Nearly half of men experience some degree of baldness by the age of 50. Experts
say they have discovered what they believe is the cause of male pattern baldness. It
is not simply a lack of hair, but rather a problem with the new hair that is made. Hair
follicles contain stem cells, but in males suffering from bald patches, these cells
function abnormally; these stem cells lose the ability to jump-start hair regeneration.
Scientists have known that these follicle stem cells need signals from within the skin
to grow hair, but the source of those signals has been unclear. Bald areas had the
same number of hair-making stem cells as a normal scalp, but there are fewer of a
more mature type, called the progenitor cell. In men experiencing baldness, this
manufacturing defect means the hair produced is so small it appears invisible to the
naked eye, giving the classic bald spot or receding hairline. Ultimately, they hope to
be able to develop a cream that could be applied to the scalp to help the stem cells
grow normal hair. This treatment is expected to work by activating already existing
stem cells on the scalp. Later treatments may be able to simply signal follicle stem
cells to give off chemical signals to nearby follicle cells which have shrunk during the
aging process, which in turn respond to these signals by regenerating and once
again making healthy hair. Most recently, Dr. Aeron Potter of the University of
California has claimed that stem cell therapy led to a significant and visible
improvement in follicular hair growth.
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The use of embryonic stem cells in medical research and therapy is highly
contentious, and raises many ethical concerns, primarily concerning the creation,
treatment, and destruction of human embryos incident to research involving
embryonic stem cells.
Many of those who support the use of embryonic stem cells would argue that
embryos are not equivalent to human life while they are still incapable of surviving
outside the womb (i.e. they only have the potential for life) and they do not resemble
the human form at this early stage. Also, more than a third of zygotes do not implant
after conception. Thus, far more embryos are lost due to chance in the females body
across the world than are proposed to be used for embryonic stem cell research or
treatments. Also, Blastocysts are a cluster of human cells (roughly 150 cells) used in
embryonic stem cell research that have not differentiated into distinct organ tissue;
making cells of the inner cell mass no more "human" than a skin cell. Some parties
contend that embryos are not humans, believing that the life of Homo sapiens only
begins when the heartbeat develops, which is during the 5th week of pregnancy,or
when the brain begins developing activity, which has been detected at 54 days after
conception. In vitro fertilization (IVF) generates large numbers of unused embryos
(e.g. 70,000 in Australia alone).[ Many of these thousands of IVF embryos are slated
for destruction. Using them for scientific research uses a resource that would
otherwise be wasted. Also, abortions are legal in many countries and jurisdictions.
The argument then follows that if these embryos are being destroyed anyway, why
not use them for stem cell research or treatments? Scientifically, there are also many
benefits of using embryonic stem cells as opposed to a stem cell in any other form.
Embryonic stem cells are likely to be easier to isolate and grow ex vivo than adult
stem cells and they divide more rapidly than adult stem cells, potentially making it
easier to generate large numbers of cells for therapeutic means; an adult stem cell
might not divide fast enough to offer immediate treatment. Embryonic stem cells also
have greater plasticity, potentially allowing them to treat a wider range of diseases.
This argument remains hotly debated on both sides. Those critical of embryonic
stem cell research point to a current lack of practical treatments, while supporters
argue that advances will come with more time and that breakthroughs cannot be
predicted. Stem cell debates have motivated and reinvigorated the pro-life
movement, whose members are concerned with the rights and status of the embryo
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as an early-aged human life. They can believe that embryonic stem cell research
violates the sanctity of life and some also view it synonymous to murder. Some
people believe that an embryo is a person with the same moral status as an adult or
a live-born child. As a matter of religious faith and moral conviction, they believe that
“human life begins at conception” and that an embryo is therefore a person. this
perspective, taking a blastocyst and removing the inner cell mass to derive an
embryonic stem cell line is tantamount to murder. Pro-life supporters often claim that
the use of adult stem cells from sources such as umbilical cord blood has
consistently produced more promising results than the use of embryonic stem
cells.[27] Furthermore, adult stem cell research may be able to make greater
advances if less money and resources were channeled into embryonic stem cell
research.
However, there are promises of a solution that would satisfy both sides of the
debate. In 2006, researchers at Advanced Cell Technology of Worcester,
Massachusetts, succeeded in obtaining stem cells from mouse embryos without
destroying the embryos. If this technique and its reliability are improved, it would
alleviate some of the ethical concerns related to embryonic stem cell research.
Some countries, because of ethical considerations, do not permit certain types of
research with stem cells. Austria, France, Germany, Ireland, do not allow the
production of embryonic stem cell lines, but the creation of embryonic stem cell lines
is permitted in Finland, Greece, the Netherlands, Sweden, Italy and the United
Kingdom. China has one of the most permissive human embryonic stem cell policies
in the world. In the absence of a public controversy, human embryo stem cell
research is supported by policies that allow the use of human embryos and
therapeutic cloning. Iran has banned embryonic stem cell lines.
In relation to religion and stem cell research, Baptists oppose human embryonic
stem cell research on the grounds that "Bible teaches that human beings are made
in the image and likeness of God and protectable human life begins at fertilization.”
However, it supports adult stem cell research as it does "not require the destruction
of embryos.” In regards to embryonic stem cell research, the Catholic Church affirms
that human blastocysts are inherently valuable and should not be voluntarily
destroyed as they are "from the moment of the union of the gametes" human
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subjects with well defined identities. The Church supports research that involves
stem cells from adult tissues and the umbilical cord, as it "involves no harm to human
beings at any state of development.
According to Jewish Law, embryonic stem cell research is permitted in Judaism so
long as it has not been implanted in the womb; not only is it permitted, but research
is encouraged, rather than wasting it.
References
www.newscientists.com/topic/stem-cells
Stem cell derived treatments for eye disease:
www.stemcells.nih.gov/research/highlights www.faseb.org
BBC news
CNN news
Use of stem cells to cure diabetes: www.diabetes.org.uk www.diabetes.co.uk
Ethics www.en.wikipedia.org/wiki/Stem_cell_controversy
www.stemcells.nih.gov/info/ethics.asp
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Conclusion
Embryonic stem cells have been promised to cure many conditions. It was our idea
to explore the future implications and contributions to medicine that the
advancements that embryonic stem cell technology would make and to consider the
ethical issues concerned with this part of pioneering fast moving are of medicine.
Stem cells have the potential to enable scientists to create new organs, regrow
crippled body parts, or reverse the damage of chronic illnesses, such as diabetes.
We have discussed the issue which scientists are faced with, with reliably directing
the differentiation of embryonic stem cell into specific cell types that may be able to
treat diseases in the future. We have described embryonic stem cells and how they
are available to be used by scientists for therapy.
The main focus for our paper has been four pioneering uses for embryonic stem
cells in modern medicine. However, it is to be advised that these are only a small
selection of the vast number of trials and research areas within embryonic stem cell
research. We discussed the potential human embryonic stem cells have in treating
blindness and vision impairment, deafness and hearing loss, baldness, and diabetes.
We have referenced the clinical trials performed by pioneering scientists and medics
worldwide for further reading.
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