Download The Application of Stem Cells in relation to potentially

The Application of Stem Cells in relation to potentially reversing the
Effects of Emphysema and providing a cure for Type 1 Diabetes
considering the ethical issues involved
By
Nikisha Sondhi
Charlotte Lokes
Katie Thompson
Pass with Merit
RESEARCH PAPER
BASED ON
PATHOLOGY LECTURES
AT MEDLINK 2011
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Abstract
The discovery of stem cells opens many doors to the numerous possible opportunities available regarding their
uses. This paper seeks to explore their current roles along with our ideas for potential developments upon
present research taking place today. We will pay particular attention to the idea of stem cells being used to
reduce both the number of sufferers with Emphysema, as well as Type 1 Diabetes. Our first proposal is to use
stem cells to help regenerate damaged alveoli in order to improve the quality of life of millions of victims with
Emphysema. We also look into the use of stem cells to help cure Type 1 Diabetes, through stopping beta islet
cells being destroyed in the pancreas. Along with these developments come the many ethical issues which
could be raised and their limiting effects upon utilizing stem cells to their greatest potential.
Introduction
Stem cells are undifferentiated cells which have the ability to differentiate into specialised
cells. There are two types of stem cells, those found in Embryos in the Blastocyst phase
(where the embryo is four to five days old), as well as Adult stem cells which can be found in
bone marrow, blood and the liver. One factor that differs between the two types of stem
cells are their potencies. While embryonic stem cells can differentiate into any cell in the
human body, adult stem cells are limited to divide and form only their cell of origin. Adult
stem cells are found in the body in a non-dividing state until they are stimulated by the
presence of disease or tissue injury however when in culture they do not have the ability to
divide indefinitely.
The inner cell mass of the Blastocyst, called the Embryoblast is where Pluripotent embryonic
stem cells are found, bearing the gene OCT ¾. This gene distinguishes them from the outer
cell mass, bearing the gene CDX 2, which will go on to form the placenta surrounding the
embryo. Embryonic stem cells are Pluripotent as they do not have the ability to become
placenta but otherwise have the ability to differentiate into any one of the 220 different cell
types that make up the human body. This characteristic therefore makes them more useful
than adult stem cells due to their wide diversity.
Embryonic stem cells are extracted from the Blastocyst and placed in a culture, rich of
nutrients, where they divide indefinitely. The stem cells do not differentiate, but simply
duplicate whilst maintaining their ability to later differentiate into any type of cell in the
human body. It is then possible to stimulate the undifferentiated stem cells to steer their
development into specific cells depending on a combination of genetic and environmental
factors acting both within the nucleus and at the surface membrane -directed
differentiation. Within the body, stem cells ability to know which cells to differentiate into
comes from the already differentiated cells sending out chemical signals (biochemical
messengers). Receptors on the stem cells recognize these chemical signals and send out
their own signalling compounds to their stem cell nucleus, resulting in specific DNA
sequences which are then translated into specific cell proteins – this enables stem cells to
differentiate into the same cell type that they are surrounded by. This property of stem cells
makes them particularly useful as they have the potential to repair damaged tissue when
under the correct conditions in the body.
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Stem cells have a huge range of medical applications due to their remarkable properties; an
example of this is the use of stem cells in the treatment of leukaemia. The stem cells used in
this example are found in bone marrow. Leukaemia is caused when leukocyte blood cells,
used to fight off infection, start to function abnormally and become cancerous. Once
cancerous they start to interfere with other organs and are unable to continue fighting
infection. Bone marrow transplants are currently the second most used treatment, behind
chemotherapy, to treat such a disease. The transplant involves finding a bone marrow
donor whose stem cells will replace those of the patients allowing healthy leukocytes to
develop and differentiate from the stem cells. Another area in which stem cells are being
used is in the treatment of multiple sclerosis. In this case Foetal stem cells are administered
intravenously and go on to detect the damage which has occurred within the body and
attempt to repair it. It is believed that the role of the stem cells in this situation is to protect
the myelin in the brain from being attacked by the body’s immune system, which essentially
will reduce the effects of multiple sclerosis as the brain will once again be able to react and
create signals to the rest of the body. Alternatively stem cells may cause a re-growth of
myelin in the brain.
Due to stem cells unique characteristics there is no end to possibilities regarding their uses
however one of the main problems occurs when it comes to transplanting the cells –
Immune rejection. The body’s immune system recognises the implanted cells as ‘non-self’
and acts to destroy them. One method to avoid this is for the patient to take
immunosuppressant drugs however this makes them more susceptible to other illness. An
alternative is therapeutic cloning which involves replacing the stem cells DNA with the
patients DNA to avoid this rejection. This can be done through somatic cell nuclear transfer,
shown in Figure 1, where the nucleus from an egg cell has been removed and replaced with
the adult cell’s nucleus. The egg will then continue to develop as normal into an embryo,
producing embryonic stem cells which are a genetic match to the adult cell donor. This
would be the ideal way to avoid rejection however it is a new method which needs further
research before it can be used extensively. Additionally this procedure holds many ethical
issues because embryos are being formed to then be killed and also this embryo, if
implanted into a woman, could technically make a clone of the adult and therefore this
brings about more controversy.
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Figure 1
Discussion
3.8 million People were diagnosed with Emphysema in the US alone in 2008. Emphysema is
a lung disease which is caused by Neutrophils from the blood making pathways through
alveolar walls. They do this in an attempt to engulf the pathogens trapped in the mucus
which is not successfully being wafted out of the lungs by the cilia because they are
damaged due to tar build up, caused most frequently by smoking. The neutrophils release
the enzyme Elastase in order to break down the Elastin fibres surrounding the alveoli,
enabling the neutrophils to enter them. However the damage done to the Elastin fibres,
reduces the alveoli’s ability to recoil and therefore they do not expel carbon dioxide from
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the alveoli sacs as efficiently. With damaged alveoli sacs the air in the lungs is not
successfully refreshed as less carbon dioxide is removed resulting in less space in the lungs
for oxygen. This lowers the bloods saturation with Oxygen, leading to fatigue,
breathlessness and rapid breathing (in an attempt to get more Oxygen to the blood).
Currently Emphysema is irreversible, once the alveoli are damaged there is no way to
reverse the damage done and eventually the sufferer will be suffocated as their lung
functionality gets weaker and weaker.
With so many people affected by this disease and so many mortalities all over the world
(see figure 2 for comparison of mortalities worldwide), it is clear that Emphysema is a
worldwide issue. Whether the Emphysema has been caused through smoking, genetic traits
or even environmental pollution from work places, stem cells could perhaps be considered
as a treatment method.
Figure 2
Embryonic Stem cells ability to differentiate into any of the 220 different cell types could
allow them to differentiate into Type II Pneumocytes when instructed to do so in order to
rebuild damaged alveoli sacs and regain successful expulsion of Carbon Dioxide from the
lungs.
Stem cells have been discovered that rapidly rebuild alveoli. First the H1N1 virus was given
to mice, resulting in great lung damage amounting to 50% loss of alveoli. However after
examining the mice 3 months later their alveoli were completely repaired. This showed that
a stem cell was regenerating and repairing the lungs. When examined through a microscope
the stem cells were dividing rapidly and travelling to the damaged alveoli where they would
create pod-like structures before becoming new alveoli.
At the Institute of Medical Biology in Singapore similar cells from human lung tissue were
isolated and it was found that the same pod-like structures were forming. Next the
signalling molecules which were causing the alveoli molecules to divide and multiply must
be identified. If the specific growth factor, which is signalling for the repair and regeneration
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of the alveoli to take place, can be isolated then this could potentially be injected into
humans suffering from lung damage to repair their alveoli. This idea could therefore be
applied to patients suffering from Emphysema where with the introduction of more type II
Pneumocytes, created through inducing stem cells to differentiate into them, could
potentially rebuild damage made to the alveoli sacs.
In order to prepare the stem cells with the necessary instructions, first a stem line would
have to be made by removing stem cells from a Blastocyst and placing them in a culture.
Once they continue to divide and replicate themselves they could be added to the specific
growth factor if it is able to be successfully identified through analysis of the above
experiment. This would allow the stem cells to differentiate into Type II Pneumocyte cells.
These cells could then be delivered by an intravenous line and hopefully help to rebuild the
damaged alveoli.
The problem with this, as with any procedure involving stem cells, is the chance of the stem
cells being rejected due to them not being an identical match. If the stem cells have been
taken from a different person, the DNA will not be a match and the body’s immune system
will refuse to accept the foreign bodies and will immediately work to destroy them. To avoid
this response from the immune system, lifelong immunosuppressant drugs would have to
be taken, however not only are they inconvenient for the patient but extremely expensive
to the NHS and can make the individual more susceptible to other illnesses (a similar effect
to HIV).
In addition, another possible future development of stem cells is to help cure type 1
diabetes. The immune systems of people with type 1 diabetes, attack and cause destruction
of the beta islet cells within the pancreas. As a result of this their bodies do not produce
sufficient or any insulin to help glucose enter the cells and so results in an accumulation of
glucose in the blood. The complications of diabetes, which arise from the abnormally high
glucose concentration in the blood, include: blindness, kidney failure, heart disease, stroke,
neuropathy and amputations. These complications have lead to diabetes causing more
deaths than illnesses such as AIDS and breast cancer. This is why it is vital that there is a
method that helps ensure the glucose concentration in the blood remains at a stable level.
Currently type1 diabetes is treated /controlled through diet, medication, exercise and
artificial insulin. The extent to which the doctors advise each of these treatments is
dependent on the severity of the diabetes and the extent of the damage to the islet cells in
the pancreas. At present some patients have pancreas transplants, however the issue with
this is that to avoid rejection patients must take Immunosuppressant drugs. These have to
be taken for the rest of their lives and so increase the patient’s susceptibility to other
illnesses and diseases. Some patients also receive islet cell transplantation, the effects of
this are that diabetics can inject much less insulin and live a more normal lifestyle. The issue
with both these transplants is that the demand for them much exceeds the availability. Only
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0.2 -0.5% of patients who would benefit from these treatments can receive them due to the
vast lack of availability.
The answer to this issue would be to create islet cells in labs and the closest method of
achieving this is by the use of stem cells. Stem cell development for diabetes treatment
could prove to be successful due to the discovery of a hormone produced from the small
intestine. The hormone has proved to stimulate stem cells from the pancreas into
differentiating into the islet cells, which in diabetics are the ones which their own body has
destroyed. The pancreatic duct cells are thought to be either capable of producing cells from
more than one germ layer or are thought to have the ability to differentiate or reverse to a
less mature cell type. Once cultured, these cells are relatively sensitive to changes in glucose
concentration in the blood. Due to the duct cells being unable to create a cell line, a biopsy
may need to be undertaken to remove the cells from the patient and culture them before
placing them back into the patient’s body.
The major advantage regarding stem cell usage is that they can be created and stored in
culture for as long as possible, however there is a lack of clarity as to whether the beta islet
cells would replicate or whether further transplants would be needed. Foetal tissue stem
cells which have been cultured into islet cells also contain precursor cells which go onto
proliferate once inside the body. This would result in increasing insulin content over a 3
month period, helping to resolve the current issue of lack of availability and would possibly
lead to reduction in the number of transplants needed before a patient is able to stop
injecting insulin. The use of embryonic stem cells in the replacement of islet cells in diabetics
could be very useful as they have the ability to be engineered, through therapeutic cloning,
to avoid immune rejection and resulting in those who receive these cells not needing to
have immunosuppressant drugs.
Although embryonic stem cells could be extremely beneficial for a whole range of medical
applications, the use of these stem cells conflict with many religious and ethical views. The
main moral objection into the use of stem cells is that we as humans have to choose
between protecting the life of the embryos or alleviating the suffering of many that could
benefit from the use of stem cells.
The main moral question that the use of embryonic stem cells raises is when does human
life start? There are a wide variety of views as to when we should class an embryo as a
human being. The first view is that the embryo is classed as a human from conception and
that they should have full moral status from this moment. People who believe this argue
that life is a continuous process and so the embryo will grow to become a human just as an
infant will grow to become an adult. This suggests the embryo should have a full set of
human rights and no one should have the choice to take away its life and so embryos
shouldn’t be used for stem cell research in any way. However, some people may argue that
the embryo doesn’t have any physical or emotional features and so can’t be thought of as a
human being, furthermore they may also argue that an embryo shouldn’t be seen as a
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human until it can survive independently and has its own thoughts, beliefs and emotions
and since an embryo doesn’t then we aren’t destroying a human, just a ball of cells.
Another view as to when the life of an embryo starts is that there should be a cut off point
after fourteen days; this is because after fourteen days the embryo cannot split and become
twins and before this date it might have failed to form at all and so may have been
destroyed anyway. Also before fourteen days the embryo has no central nervous system,
and therefore can’t feel pain and so it is acceptable to use the embryo for medical
applications. It is argued that as we take organs from patients that are considered to be
brain dead, there is no reason why we shouldn’t be able to use embryos for stem cell
treatments.
On the other hand, some people disagree with this and believe that life has a value to the
embryo itself and could grow into a human who should be allowed the right to live the life
that it wants. Besides, a person who has lost nerve cells in a stroke is still classed as a human
although they have reduced senses and so why should we not class an embryo as a human
because they have no feelings? If we aren’t sure as to whether to class an embryo as a
human being or not then we shouldn’t kill it.
Another ethical issue that is raised by embryonic stem cell treatments is the problem of who
should have access to the treatments. Initially the cost of treatments would be high and so
only the wealthy would be able to afford the procedures, however this would result in some
people who are more in need of the treatments not being helped due to lack of money.
Additionally, there would be restricted availability of treatments due to the restricted
availability of stem cells and so how do we assess who is more deserving of the treatments?
Do we determine this by who is suffering the most, or whose lives could be significantly
changed by the procedure?
However, the availability of embryos could be increased if medical departments were willing
to pay for the embryos from healthy donors. Conversely, this may lead to an increase in
disadvantaged women putting themselves though invasive Oocyte extraction in order to
earn some money, which again raises more ethical issues.
Although the use of embryonic stem cells could drastically change thousands of people’s
lives and significantly evolve medicine, it is impossible to progress until we agree as to when
the life of an embryo begins and when it is acceptable to take this life away. All ethical
issues must be resolved before we can continue to develop stem cells uses.
A possible solution which could potentially eliminate every ethical issue could be ‘Induced
Pluripotent Stem cells’ (IPSCs), which are formed from already differentiated cells.
Effectively, they are reprogrammed to reverse the stages of differentiation by returning to
their original undifferentiated form. This avoids ethical issues because they form embryonic
equivalent stem cells without taking cells from embryos. IPSC’s have successfully been
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created which hold the same markers as embryonic stem cells, as well as the same genes,
and they grow in the same way too. However, more research and trials need to take place
before this method can be used, to ensure their safety and efficacy.
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References
What Emphysema is, symptoms and effects caused by it, as well as statistics relating to the number of
sufferers, information from ‘www.about.com’
http://copd.about.com/od/whatisemphysema/a/emphysema.htm
http://quitsmoking.about.com/od/respiratorydiseasecopd/a/emphysema.htm
Mortality statistics of cases of Emphysema – displaying that it is a worldwide issue. Original source was World
Health Organisations Statistical Information System
http://www.nationmaster.com/red/pie/mor_emp-mortality-emphysema
What stem cells are, where they are derived from and their abilities
http://www.medicalnewstoday.com/info/stem_cell/
How and why stem cells differentiate
http://answers.yahoo.com/question/index?qid=20080920170337AAkuMaS
Animation on how embryonic stem cells are made, their extraction from the embryo and their development
http://www.dnalc.org/resources/animations/stemcells.html
How stem cells work – the ability they have to treat different diseases
http://science.howstuffworks.com/environmental/life/cellular-microscopic/stem-cell5.htm
How stem cells can be used in treating leukaemia
http://learn.genetics.utah.edu/content/tech/stemcells/sctoday/
New Scientist – How stem cells can be used to treat lung problems
http://www.newscientist.com/article/dn21102-stemcell-find-breathes-new-life-into-lung-repair.html
How stem cells can be used to help treat diabetes
http://www.wired.com/medtech/health/news/2002/09/55239?currentPage=all
http://stemcells.nih.gov/info/scireport/chapter7.asp
http://abcnews.go.com/Health/DiabetesResource/story?id=4318544&page=2
www.eurostemcell.org
http://learn.genetics.utah.edu/content/tech/stemcells/sctoday/
The use of stem cells in the treatment of multiple sclerosis
http://www.medra.com/multiplesclerosis1.html?gclid=CNvnkayZ4q4CFQ1lfAod4jQiXg
http://www.bbc.co.uk/news/health-14332206
http://www.mssociety.org.uk/ms-research/new-and-potential-treatments/stem-cell-therapy
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The ethical issues surrounding stem cell usage and the problems that arise because of them
http://www.biotechnologyonline.gov.au/human/ethicssc.html
Source of Figure 1 as well as information on types of stem cell therapy to avoid immune rejection
http://www.science.org.au/nova/079/079key.htm
International society for stem cell research – Stem cell rejection due to immune response
http://www.isscr.org/public/SC_rejection.pdf
Type 2 Pneumocytes and their ability to repair alveoli
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650613/
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Conclusion
In conclusion, there is room for development of the research currently taking place
regarding reversal of Emphysema as well as Type 1 Diabetes however there are also a
number of problems which might limit progress. One of the main worries that could arise
from the use of stem cells to treat Type 1 Diabetes is the fact that there is still nothing to
prevent the body destroying these islet cells again, just as they did to the body’s own and
original islet cells. Due to this it may prove more successful to use this treatment on type 2
diabetics, who just have a ‘blockage’ - a lack of insulin is produced but their immune system
hasn’t destroyed the cells like that of type 1 diabetics.
Another issue which lies in the way of improvement is that the islet cells which are
produced can be very insensitive to changes in glucose concentration levels in the blood,
thus making the islet cells not completely effective.
One of the main problems with using stem cells to cure Emphysema is that it holds many
specific Ethical Issues. Between 80-90% of sufferers have acquired the illness due to
smoking – some have been affected by passive smoking but the majority have made a
choice to continue smoking despite understanding the consequences. Stem Cells are
incredibly valued and require very expensive procedures. The question is, if stem cells are
one day able to treat Emphysema successfully should people who have knowingly chosen to
smoke be offered stem cell treatment to help improve their quality of life in this way?
Alternatively many smokers could argue that they have not knowingly chosen to smoke but
instead are addicted and are not physically able to stop. This brings about the issue of
ethics. Some people believe that using an embryo as the source of stem cells is taking the
life of an unborn child who has equal rights and not given their consent for their life to be
taken. In this case would it be right to take the life of an unborn child and give it to a smoker
who understands that what they are doing is gradually killing them, but chooses to do so
anyway?
There are also many other common issues which arise from the use of stem cells in
treatments for most diseases. These are things such as rejection from the body where
immunosuppressant drugs have to be taken which themselves possibly have more
damaging effects than the illness being treated. To avoid this in the future embryonic stem
cells can be engineered to avoid rejection, however this also leads to the great ethical
debate, which up to now has been the main hindrance in the development of stem cells.
The future of stem cells is very bright and the possibilities of their uses could prove vital in
the future of the medical world, however at this current moment it is very difficult to
develop uses of the stem cells with lack of clarity and contradiction from elsewhere. The
main reason that stem cells are not being used to their full effect is due to ethical issues and
worries regarding the future implications of treatments with stem cells.
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