HOW EMBRYONIC STEM CELLS CAN BE USED TO TREAT HEART
DISEASE
By
Rida Rizvi
Nayyab Butt
Pass with Merit
RESEARCH PAPER
BASED ON
PATHOLOGY LECTURES
AT MEDLINK 2011
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ABSTRACT
Today, in the 21st century, human diseases, such as Parkinson’s, Alzheimer’s and heart disease
continue to prevent people of their right to health; diseases deprive people of mental, social and
physical wellbeing. However medicine is advancing at a startling rate and treatments of diseases that
did not exist a few years ago now do. Now, with research into the use of embryonic stem cells, there
is the prospective to spectacularly alter approaches to understanding and treating diseases and to
alleviate agony of a patient. Recently techniques of in vitro fertilisation have taken place providing an
unparalleled prospect for understanding the development and use of embryonic stem cells. This
research paper aims to explain this and the positive potential uses of embryonic stem cells in
medicine specifically for cardiac regeneration e.g. following a heart attack, along with the other vast,
rather controversial issues surrounding it, for example ethical issues.
INTRODUCTION
In the world of medicine today the advances are beyond imaginable, for example the
discovery of antibiotics by Alexander Fleming has significantly improved health of
people everywhere in the world. Medical technology has also been developed and
enhanced, for example robotic surgeries; which overcome the limitations of
minimally invasive surgery. The common factor of all the advances in medicine that
have taken place is that they improve patients’ lives.
In medicine the idea that stem cells can treat a number of congenital and
degenerative diseases for which there are no cures as yet is extremely enthralling. At
this moment in time we are living in a world in which we have the technology and
money to carry out research into stem cells and into what could be yet another life
changing chapter in medicine. So, why not make use of the resources and
opportunities we have to alter and save even more lives? Let’s not just cure
symptoms but treat the actual problem.
Embryonic stem cells can revolutionise the history and future of medicine; with
incurable diseases becoming curable.
The purpose of this research paper is to examine the use of embryonic stem cells in
the specific field of cardiology i.e. how to treat patients with heart disease. This
specific topic has been chosen
because in the UK the highest
mortality rates are due to ischaemic
heart disease, with 17.4% male deaths
and 12.1& female deaths (1). ‘Heart
attacks and congestive heart failure
Figure 1
remain among the Nation's most
prominent health challenges despite
many breakthroughs in cardiovascular
medicine.’ (6)
Embryonic stem cells are derived from
embryos can be obtained from a
human embryo or via ‘in vitro
fertilisation’ (3).
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In IV clinics, multiple donor eggs are fertilised to increase the chance of an egg
actually being fertilised and then once fertilisation has occurred it is allowed to
divide by mitosis. The idea is to produce ‘viable blastulas’ from which the inner cell
mass is extracted. The inner cell mass can be picked up using a pipette, they are then
transferred to a petri dish for culturing. The blastula can be implanted in the uterus
of the egg donor to produce a human embryo. (9) Many embryos produced are not
clinically used so may be discarded if not donated by donor parents for research. The
embryos from which embryonic stem sells are derived are around 5 days old only
and are am empty ball of cells called a ‘blastocyst’. Figure 1 shows a fertilised egg
developing into a blastocyst which is not a human foetus as yet. The blastocyst
consists of two primary cell types of which the inner cell mass is used in the research
(the trophoblast develops to form the placenta). (8)
In ‘in vitro fertilisation’ embryonic stem cells are grown in a cell culture in a
laboratory setting and not from eggs fertilised in a woman’s body. They have the
unique ability to differentiate to form any cell, tissue or organ; they are the most
pluripotent stem cells that exist. (See figure 1) Human embryos can be donated to
researchers having given a fully confirmed consent. ‘…two appropriate potential
sources of donation are embryos with poor quality that makes them inappropriate
for transfer and embryos remaining when couples have definitely completed their
family and do not wish to donate the excess embryos to others.’ (5)
Embryonic stem cells are valued a lot in medicine because they unite many
properties not found together in other cells, such as in adult stem cells or blood cells.
Embryonic stem cells can self-replicate for an indefinite period ‘without death or
mutation’ (5) which means they are available on a large scale for research purposes.
Since they are unspecialised and can differentiate into any type of cell/tissue/organ
they are very useful in treating heart disease. ‘Unlike muscle cells, blood cells, or
nerve cells—which do not normally replicate themselves—stem cells may replicate
many times…the cells are said to be capable of long-term self-renewal.’(3)
In 1998 James Thomson isolated and cultured mouse embryonic stem cells. His
research shed light on the fact that embryonic stem cells are capable of developing
into any type of specialised cell so are sources of tissue repairment and cell
replacement. (10)
Since this a lot of research has been carried out into the use of embryonic stem cells
and a trial, known as the Moofields Trial. It was described as "another milestone for
the field of regenerative medicine". This research has given patients a lot of hope
and there is a lot of optimism too as it has the potential to treat people with
advanced Stargardt disease. This is a macular degeneration which causes disabling
loss of sight in young people. However the trial showed that embryonic stem cell
therapy has the potential to treat various diseases, e.g. diabetes and cancer. In the
trial, retinal cells produced from stem cells were injected into the retina of the
patient during the operation. (11)
Along with transplantation therapies, embryonic stem cells can serve as model
systems for understanding the biology of human development and the diseases that
are caused due to defective human development. Cells from the blastocyte can be
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used to several other things, for example for drug discovery and for testing the
toxicity of other drugs like alcohol. This is all possible because human embryonic
stem cells are human cells which possess membrane bound receptors on their cell
surface membrane. This breakthrough has proved very useful because human cells
are more apposite as test models and the use of drugs are intended for human
patients so testing for drugs on animals cannot always be generalised to humans due
to obvious differences. (2) This means to stay that instead of testing side effects of
new drugs on humans directly, they can be tested on human embryonic stem cells
instead. ‘Other kinds of cell lines are already used in this way. Cancer cell lines, for
example, are used to screen potential anti-tumor drugs. The availability of
pluripotent stem cells would allow drug testing in a wider range of cell types.’ (3)
By looking at human development by examining embryonic stem cells, information
about complex events that occur during human development can be found such as
how undifferentiated stem cells may form an organ, such as the heart. Many things
can be found out, such as what stimulates the stem cells to develop into a certain
cell or organ- by cell communication or spontaneous mutations, for example.
Therefore if scientists know how diseases such as cancer are caused then attempts
can be made to prevent it and new ways can be found to treat it for example it may
be that a certain gene is on that should be off or vice versa.
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DISCUSSION
One of the main problems with embryonic stem cells, apart from ethical issues, is
the chance of rejection of the tissue or organ created for the patient. Embryonic
stem cells can trigger the immune response. This was found in mice studies where
‘the immune systems of mice injected with human embryonic stem cells attacked
the cells, which died within a matter of days. Even when treated with anti-rejection
drugs, the cells proliferated for only 28 days before they also died (9)’. This happens
because the embryonic stem cells are not from the persons own body, which means
that the immune system detects the cells as foreign and as a threat so will try to
destroy the cells. Here, adult stem cells and tissues derived from them have an
advantage as they are derived from the patients’ own body so there is less chance of
rejection after the transplantation. As embryonic stem cells are very important and
represent the future of medicine for many, there have been attempts to reduce the
chances of rejection. One way to do this would be to give the patient
immunosuppressants drugs however these drugs can have damaging side effects, for
example they increase the chance of infection by pathogens, may cause swelling by
causing fluid retention and increase the chance of uncontrolled bleeding.
Another way to reduce rejection was found by the ‘International Stem Cell (ISC) Corp
who derived four unique embryonic stem cell lines that open the door for the
creation of therapeutic cells that will not provoke an immune reaction in large
segments of the population (10)’ this is possible because the stem cells have been
modified to have a ‘simple genetic profile (10)’ in the part of the DNA that codes for
immune rejection. This groundbreaking research has made it possible for embryonic
stem cells to be used to treat a large number of patients one day. Rejection of the
embryonic stem cells can be a big and difficult issue to deal with. However when you
think of the possibilities that stem cells hold it is a small issue in comparison and with
the new research that makes it possible to produce cells that will not be rejected by
the patient’s immune system, we are one more step closer to using embryonic stem
cells to treat a number of life altering diseases.
One more problem found from embryonic stem cell research is that the stem cells
can grow into tumours; however scientists and supporters of embryonic stem cell
research say that this kind of problem is very rare and a lot is being done to solve the
few examples that have developed into tumours.
Myocardial infarction and heart failures are the main causes of death in developed
countries such as the UK. Heart disease cause the muscle cells damage or even kill
them. Myocardial infarction is caused by ‘interruption of blood supply to a part of
the heart, causing heart cells to die. This is most commonly due to occlusion
(blockage) of a coronary artery (12)’ unlike other cells heart cells cannot regenerate
after being destroyed. The heart is said to be myogenic which means that it can
initiate its own contraction. The cells that compromise cardiac muscle are known as
cardiomyocytes. Cardiac muscle cells or cardiomyocytes rely on a good oxygen
supply which is fulfilled by the coronary arteries. Blockage of these coronary arteries
can lead to heart attack and further the death of cardiac muscle.
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In this article we are looking at the possibility of using embryonic stem cells to
regenerate cardiomyocytes. As the heart cannot repair itself the only way to treat a
heart attack currently is through major surgery such as a heart transplant. However
there are many disadvantages of heart transplants such as it is invasive, a major
operation is required, there are chances of rejection and the patient has to take
immunosupressant drugs for the rest of their life. Another reason is that there is a
shortage of donor hearts so if a replacement is not found straight away it can lead to
worsening of the patient’s condition. This is where stem cell research becomes
important. Two other types of cells excluding cardiomyocytes are required for the
heart to function properly, these are: vascular endothelial cells which form the inner
lining of the new blood vessels, the other is smooth muscle cell which forms the wall
of the blood vessels. Embryonic stem cells are able to differentiate into relatively
large numbers of early stage cardiomyocytes that functionally integrate with host
heart cells (11). This means that all the types of cells required for a part of the heart
to regenerate can be extracted from the embryonic stem cells.
This treatment is in its early stages at the moment with experiments being carried
out on animals. The treatment is not yet progressing for a number of reasons such as
people object to the use of embryos just for the stem cells as they believe that the
embryo is a form of early life. However scientists would argue that the potential out
weighs the disadvantages by saying that the embryos would have gone to waste
otherwise and the treatments from embryonic stem cells could be life changing. We
would also be able to learn about the complex development of humans through
embryonic stem cells which could lead to many other developments in medicine.
The embryonic stem cells used in research are taken from embryos that have been
discarded from in-vitro fertilisation for a number of different reasons. This means
that the embryos would go to waste otherwise. Helping to progress stem cell
research could be a use for them rather than simply discarding them. Embryonic
stem cells are grown from cells found in an embryo which is only a few days old.
There are many different religious views on embryonic stem cell research. Christians
believe that life begins at conception and there is no such thing as pre-embryo. This
means that they believe that using an embryo for extraction of the cells is like taking
a life. They believe that ‘at the moment of conception, the embryo is 100 percent
human, with all 46 human chromosomes and a fully functioning, unique genetic
code. Size and location do not determine humanity (12)’. On the other hand other
religions such Islam and Judaism encourage stem cell research, as they believe that
saving a life is important. Islam believes that an embryo ‘has the potential to grow
into a human being, but it is not yet a human being’ (13). Judaism says that the
embryos donated from in-vitro fertilisation are ‘early embryos with no real life
potential at all and they're not considered alive. Consequently, there would be no
Jewish legal opposition to disposing of them, researching on them, or deriving stem
cell tissue from them’ (14). This view had lead to THE ISREAL RESEARCH STORY.
6
In recent years there have been many advances in the research of embryonic stem
cells even with the restrictions from the government. As embryonic stem cell
research is an ethical and much debated about issue it is not as well funded in the
UK. However in other countries such as Singapore the laws are less strict which
makes it easier for the researchers to gain embryos .This means that they have a
larger number of embryos from which they can extract embryonic stem cells. They
have, right now, six stem cell lines made from conventional, non cloned embryos.
Now it is perfecting methods of turning those cells into the kind of pancreatic islet
cells that diabetics need, as well as into heart muscle cells that could help heart
attack patients. The company is developing new, mouse-free culture systems and
sterile production facilities (15). In UK at the moment it is legal to create cloned
human embryos but only for medical research, this is a leap forward as it would
mean that the researchers will have more embryos to research on. Also if the
embryo is cloned from the patients own DNA there is a very little chance of rejection
when the cells are injected into the body (15). There have been trials of embryonic
stem cell treatment in humans in the UK. As mentioned before, stem cells have been
injected into the eyes of young patients who have a disease called Stargardts
macular dystrophy which can cause blindness from a young age. Patients taking part
in the UK trial will have between 50,000 and 200,000 cells injected behind the retina
through a fine needle in an outpatient operation expected to take up to an hour.
Only patients with advanced disease will be admitted to the trial.
The University of London in association with Barts Hospital carried out a study into
whether damage to the heart caused by a heart attack could be reversed by injecting
stem cells taken from the patient’s bone marrow into their heart quickly after the
attack.
In the project the aim was to see if stem cells could speed up recovery after a heart
attack as well as reducing the risk of another attack to reduce deaths. Half the
project has been completed now and it verified that the researchers are able to
deliver stem cells more quickly than anyone has delivered before i.e. within 6 hours
of the myocardial infarction. In addition it was found that no unexpected
implications occurred so it proved that stem cells are a safe and reliable source of
treatment for heart disease.
Currently there are only two universities involved in this trial but due to the success
of the project the clinical value and life changing aspects of stem cells has been
recognised by other UK and European hospitals.
There is an ongoing debate about whether adult stem cells should be used or
embryonic stem cells.
Possibilities to cure other diseases without the controversial use of embryonic stem
cells include the use of cells from one’s own body e.g. recently in the news it has
been shown that a young boy who got burned severely was treated by using stem
cells from his shoulder which multiplied and were transferred to a spray can; these
cells were sprayed on to the burn and the boy’s damaged skin was self-renewed.
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In animals stem cells from the bone marrow have been seen to create blood vessels
and new myoctyes.
Adult stem cells are less resourceful than embryonic stem cells due to their lack of
ability to differentiate into any type of cell. However adult stem cells are more easily
accessible than embryonic stem cells because adult stem cells can be obtained from
various parts of the body such as the nose, pancreas and bone marrow; whereas
embryonic stem cells must be obtained through in vitro fertilisation. This brings with
it many ethical issues as explained throughout this research paper. On the other
hand embryonic stem cells are capable of unlimited cell division so it may turn out
that more embryonic stem cells are produced anyway, than the adult stem cells
extracted. Adult stem cells do not multiply readily which creates difficulties in using
them for therapeutic cloning. Plus they are more likely to have abnormalities from
DNA mutations. Another factor affecting their use is the age of the stem cells; the
older they are the less capable they are of differentiating. Embryonic stem cells are
brand new cells and can self-renew more easily and quickly.
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http://www.explorestemcells.co.uk/adultvsembryonicstemcells.html
The article, ‘Stem Cell Research and Applications’ produced by the American
Association for the Advancement of Science and Institue for civil society.
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8. http://en.wikipedia.org/wiki/Blastocyst
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14. http://stemcells.nih.gov/info/basics/basics3.asp
15. http://www.explorestemcells.co.uk/adultvsembryonicstemcells.html
16. http://www.medicalnewstoday.com/releases/128516.php
17. http://www.sciencedaily.com/releases/2005/10/051012084443.htm
18. http://www.lifenews.com/2007/01/08/bio-1940/
19. http://www.guardian.co.uk/science/2011/may/13/stem-cell-transplantsrejected-ips
20. http://www.nrlc.org/news/2008/NRL09/StemCells.html
21. http://www.sciencedaily.com/releases/2007/12/071220123837.htm
22. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.001
1536
23. http://www.gotquestions.org/Christian-stem-cell-research.html
24. http://www.islam101.com/science/stemCells.htm
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26. http://science.nationalgeographic.com/science/health-and-humanbody/human-body/stem-cell-divide/#page=1
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CONCLUSION
This research paper has shown that embryonic stem cells are the future of medicineespecially for the regeneration of heart muscle. Although adult stem cells are
obtained for the patient from the patient’s own body, there is no risk of rejection or
an immune response being triggered but they are much less useful than embryonic
stem cells. Embryonic stem cells are not compatible on bodies other than from
where they were obtained. As a result they put a patient’s life in danger as
microscopic diseases may be transferred from the transplanted cells to the body’s
cells.
Embryonic stem cells are not being used to treat heart disease currently. This is
because of the ethical issues surrounding the use of embryonic stem cells as well as
the practical inconvenience; such as the risk forming a tumour. However this
problem has been addressed and the embryonic stem cells can differentiate into
specific cell types first e.g., cardiomyocytes to reduce the risk of tumours known as
teratomas developing.
However the side effect that worries people most is the unseen possibilities of a
random mutation.
People who require a heart transplant may have to wait many months or years for a
suitable heart, in this time their condition may worsen and more arteries may
become blocked. Risks of other diseases will increase too, such as kidney or liver
disease or a stroke. In this sense it is much more convenient to use embryonic stem
cells to produce the cells and tissues needed for repair. This is much more
convenient in the long term.
At the moment people are realising the potential of embryonic stem cells so it is
possible that with time the ethical issues debate will be resolved as it is becoming
clear that the advantages far outweigh the disadvantages. Therefore it is suggested
that further research should take place to see how a heart muscle can be
regenerated effectively. If successful, the procedure could be universalised. It is also
possible, that in the rapidly changing world of medicine, new discoveries will be
made e.g. how to obtain embryonic stem cells without destroying an embryo. It is
possible that we will be able to predict how the heart will function, with its new
myocytes developed from embryonic stem cells, inside the body. In addition to
embryonic stem cells it is vital to continue research into adult stem cells that involve
less controversial issues as they can be obtained from a human without harming
them in any way. Both the methods will revolutionise medicine and may be the
precious way in which to save more lives.
Embryonic stem cells are like a miracle; unless researchers do not carry out more
practical research there is no way of telling their potential. Curing heart diseases
would be a turning point in the UK’s health history.
The path of embryonic stem cells exciting yet unpredictable due to the nature of
their course. One thing is certain: embryonic stem cells can treat diseases but this
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will not happen easily so the scientific breakthrough may come across complications.
For many people, especially doctors and researchers, this is one amazing incentive.
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