Download Stem Cells: Research for potential use in treating

Stem Cells: Research for potential use in treating Myocardial
infarction injuries
Figure 2: Figure A shows a heart with dead heart muscle caused by a heart attack. Figure B shows a coronary artery with
plaque buildup and a blood clot.
By
Abubakar Shahid
Daniel Brierley
Pass with Merit
Research Paper Based
On Pathology Lectures
At Medlink 2011
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Abstract
Stem cells have amazing potential in the treatment of heart related diseases as they can
differentiate to become specific cells and repair, or differentiate into cells that have been damaged
by disease, and then carry out the particular function required. In this paper, we will be discussing
the latest research on how stem cells are being and our view on how to use stem cells for treatment
and look at a variety of social and ethical issues around stem cell research.
Introduction
The magnificent potential of stem cells was first discovered by Ernest McCulloch and Dr. James E. Till
in the 1960’s [14]. They were the first to develop the clonal method to identify stem cells and further
used these techniques to establish the studies on stem cells. They were very well known for their
studies and with the limited technology of the time, they managed to discover that stem cells could
be found in embryos as well as tissue.
Embryonic stem cells are defined as: “Cells obtained
from an embryo in the blastula phase, when they are
only a few days old. Because they have only begun to
differentiate, these cells have the capability of
developing into any cell in the human body, a fact
which makes them potentially important in
medicine.”[1] This infers that: the cells made by a
fertilised egg have yet to differentiate into different
cell types. The blastula phase (see figure 1) is the part
of the embryo’s development where the cells are
pluripotent, they can differentiate into every type of
cell in the human body at this particular stage.
Stem cells can be isolated from the blastula, and
specially come from the inner cell mass. They are
Figure 1: Early blastula phase
then grown in a culture dish until there are
enough to stimulate the specialisation of the cells.
Alternatively, they can be taken from an adult by
extracting them from the many tissues they are found in. This requires an operation to remove the
stem cells so that they can also be grown in a culture dish. Embryonic stem cells have a major
advantage over
adult stem cells as they can change into any type of
cell in the human body known as pluripotent cells, whereas adult stem cells
are restricted to the tissues they are found in. The
use of stem cells medically is increasing and solutions are being found to the most abundant
diseases such as Alzheimer’s, Parkinson’s, diabetes, myocardial infarction etc.
Myocardial infarction, commonly known as heart attack is currently the leading cause of death in
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both in men and women worldwide. It results from a blockage in the coronary artery usually caused
by a large blood clot. Usually a blood clot isn’t a problem, but when the coronary arteries are already
partially blocked by plaque due to high blood cholesterol level, the clot will fully block the artery.
This in effect starves the heart of oxygen and reduces blood supply, causing the heart cells to die.
After recovering from a MI the dead heart cells grow back as scar tissue which is unable to function
like normal heart tissue. Therefore, this makes it much harder for the heart to pump blood around
the body causing heart problems for the rest of their lives.
After discovering that trials have been undertaken to reduce scar tissue from the aftermath of heart
attacks reported in the ‘Lancet medical journal’, we have researched the potential treatments for
myocardial infarction injuries using stem cells and now undertaken a “Gedankenexperiment” to see
the possible solutions. At the moment we are fully aware that the safety aspect has not been
evaluated for this treatment and there may be various ethical issues which arise against the
treatment. However if such treatment appears to be successful, then it will be a promising result to
help millions and more sufferers around the world.
Discussion
Myocardial infarction is a serious threat and a leading cause of death in both, men and women.
Epidemiology suggests that heart disease causes 1 in 5 deaths in USA and 25000 people die every
day of a heart attack [3]. This clearly tells us that the threat of this disease is vast. It is caused, mainly
by blood clots that block the coronary artery, starving the heart muscles of oxygen. The rising rate of
obesity and blood cholesterol levels has increased the number of heart attacks suffered each year.
After suffering from a heart attack, depending on severity, the affected muscle cells die and form
scar tissue, making the heart far less efficient. [12] However, trials using stem cells are being taken on
possible solutions for treatment post myocardial infarction.
Induced Pluripotent Stem (iPS) Cells
Induced pluripotent stem cells are defined as: “somatic cells
that have been genetically reprogrammed, in such a way that
they lose their tissue-specific qualities and become
pluripotent”[15]
Scientists from Mayo Clinic in Rochester, Minnesota have
developed and are currently testing Induced pluripotent stem
cells [4] which have been converted from adult stem cells that
Figure 4: Induced Pluripotent Cells
were reprogrammed fibroblasts. They believe that the cells
developed will replace scar tissue after a potentially fatal
heart attack and become a type of cell that repairs damage to
the heart. The beauty of using iPSs is that they’re developed from a patient’s own somatic cells so
this means that there would be a limited chance of an immunological response. This method was
first tested on mice by transplanting it in a damaged mice heart. It was reported that the response
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was extremely successful as the mice heart had improved in terms of structure and function. The
issue that arises about using this method is about how safe the procedure is. Currently it is only
being tested on mice, not on human. This suggests that the safety aspect is uncertain and the teams
aren’t prepared to take on the risk.
The name given to stem cells is prochymal. One of the most interesting properties of prochymal is
that they are universal donor cells, so they don’t require matching DNA with the patient, making
application of the treatment easier. They are also testing various application methods such as
intravenous injection, which would be far easier to do than keyhole surgery.
Researchers for the University of Minnesota have made a recent breakthrough creating a whole
heart from stem cells. [9] A major advantage over donor hearts because a donor heart will be rejected
by the immune system and the patient will have to take immune suppressant drugs for the rest of
their lives. The created heart can be made using the patients own stem cells making the chance of
rejection very slim. The new heart is created by removing the muscle cells in a donor heart using
detergents. Then stem cells are added to this extracellular matrix, which then makes the stem cells
specialise into cardiac muscle cells for the heart. This procedure has already been tried on rats and
has worked very well, due to there being no complications and the hearts being successfully
implanted. A similar technique has also been attempted on a ten year old boy to replace his trachea,
[13]
replacing a heart is looking very promising for the near future. However the procedure is being
held back because doctors don’t know how safe the procedure is going, clinical trials cannot be
started until the procedure meets safety standards. [9]
British researchers from Harefield hospital managed to grow tissue that functions in the same way as
heart valves. This exciting find will allow people with valve problems the option of having them
replaced instead of having a donor heart or using implanted valves; they need to be replaced every
few years due to the immune system attacking organic valves, or mechanical valves running out of
battery. The team extracted the stem cells from the bone marrow and specialised them into heart
valve tissue. Using collagen scaffolds the tissue can form into the correct shape for the heart valves.
The procedure has not been declared safe enough for use on patients, however trials on pigs and
mice will give doctors a better understanding on how this procedure could be used on humans. [10]
Our development
Considering all the research and current techniques into stem cells and treating the heart post
myocardial infarction, we think they can be applied to helping people recover fully from problems
with the heart from having a myocardial infarction, particularly repairing the dead cells to improve
the overall efficiency of the heart. We are also considering any possible social and ethical issues and
how they may impact on different people.
After a patient has suffered from a MI we suggest creating a collagen mould by scanning the patients
heart to find out where the dead cells and scar tissue. After modelling the collagen, stem cells can be
taken from the patient’s heart and cultured into the mould. When the cardiac tissue starts to form
on the mould the new cells can replace the scar tissue formed on the outside of the heart via open
heart surgery. This will make the affected part of the heart more stable and more able to pump
blood around the body, which leads to a healthy heart and a healthier patient. Since induced
pluripotent stem cells may have the ability to replace the scar tissue of their own accord it may be
possible to simply insert the stem cells onto the scar tissue directly allowing them to replace the scar
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tissue on their own. This could be done by keyhole surgery by inserting the cells directly onto the
affected heart area. This would require a surgeon with a high degree of skill due to the tiny room for
error in the operation.
A simpler but less effective method is intravenous injection where the iPs cells are injected via the
veins. The cells will then pass through the heart and recognise the scar tissue. The cells then
differentiate to replace the scar tissue. This will require multiple treatments depending on the
extent of the heart damage, but is a lot less risky and will not require the patient to stay in hospital
while recovering from the operation.
Sometimes the heart is so badly damaged it needs a transplant, or parts of the heart need to be
replaced. This could be done by again creating a collagen mould for the stem cells taken from
various tissues in the body: like inside the bone marrow; or iPs cells to be inserted into. This would
develop the specified tissue needed for the heart. This can be used to repair specific valves or
coronary arteries on the heart. When growing a whole heart though the collagen mould would not
be sufficient, as the heart has many different types of tissue it needs to form so it would be a better
idea to get a extracellular matrix made form a donor heart or a pigs heart and removing the heart
tissue from the donor heart using detergents. This would create a scaffold for the stem cells to be
put into. By introducing the stem cells into the scaffold the cells should then start to divide into their
specialised tissues, like veins, arteries and cardiac muscle. The growth of the new heart should be
carefully monitored to make sure that the correct tissues form in the correct places. Also the
scientists should make sure that the cells have the right amount of their essential nutrients to
perform mitosis and other functions. This would require careful monitoring of the new heart. The
heart then can be replaced by the new heart made from the patient’s own stem cells by the normal
procedure for replacing their heart with a donor heart, which would require open heart surgery. The
cells of the donor heart should be attacked by the immune system of the donor heart, however this
will not be a problem as the stem cells would have already replaced the cells used from the donor
heart meaning the patient have no need to take immune suppressant drugs, allowing them to live
more comfortable life. This will also benefit the hospitals funds because after treatment with the
stem cells, patients are less likely to return due to further heart problems, in comparison to them
being discharged with a partially damaged heart.
This procedure should be applicable to almost all organs and tissues so can be used to treat
a variety of conditions. By making an extracellular matrix from any organ and getting the
right types of stem cell from a patient the organs can be made. By making the organ out of
embryonic stem cells would be an even bigger benefit as these cells are pluripotent so it
would be a lot easier to specialise into organs. The problem with this is that any organ given
to a patient will eventually be attacked by the immune system causing it to need a
replacement every 10 years or so, also the patient must take drugs to weaken the immune
system so it therefore makes them more prone to infection. We could take one of the cells
of the patient and by using a genetic engineering technique the DNA of the stem cell could
be removed by restriction enzymes, and replaced with the patients DNA by using the
enzyme ligase, making a pluripotent stem cell with the patients DNA. The same procedure
described before would make it possible to grow any organ using the patients DNA. [11]
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Social and ethical issues
One of the main issues is animal testing, it’s seen unethical to experiment on animals as it is seen as
cruel. Experimenting on animals is an essential part of stem cell research as many proposed
treatments must be safe enough not to cause any harm to a patient. The best way to try out new
treatments is with animals such as mice. There is argument for both sides, however further stem cell
research could lead to animal testing to be lowered considerably. This is because scientists can grow
specialised tissue from stem cells which can then be tested with treatments without the use of
animals. This would give a greater degree of accuracy and safety to the potential treatment.]
This leads on to another ethical issue as stem cells come from an unborn embryo, as stated in the
introduction. Many people believe this is
effectively taking away the embryos chance of
life. Most embryos developed are donated
towards stem cell research, although if stem cell
treatments are fully developed in the future then
more of these donors need to be found which
may be an issue because they’re not widely
available. [7]
Stem cell research also has many social issues. If
we look at embryo stems cells globally, many
countries will completely disagree due to religious
beliefs. Therefore we must take into
consideration, people’s social and ethical values.
Also another social issue is job losses. Healthcare
assistants and nurses with be needed less
because the recovery time of patients will be
decreased rapidly. Nevertheless, this is a
secondary issue and could be dealt more near the
time.
Figure 3: Using mice to research into stem
cells
If stem cell treatments do reach their full potential
then healthcare in the country will improve
noticeably curing people of many life changing diseases giving people a chance to live a better life as
they are potentially able to cure Parkinson’s, Alzheimer’s, spinal cord injuries and many others. [8]
This will increase the average life expectancy and will improve many people’s quality of health.
Stem cell research may have many economical benefits because the time spent in hospital after
treatment will be decreased, compared to the current recovery time after operations. As a result,
more beds will be available so the hospitals will have to spend less money on providing healthcare to
patients after operations so more funding can go into other areas of the hospitals, such as new
equipment and facilities. Another advantage is that patients will spent a short time on waiting lists
for minor operations as more beds will be available. Although stem cell research may be regarded
as unethical, their advantages to medicine outweigh the ethical issues.
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Conclusion
In conclusion, we believe that stem cell research in treating myocardial infarction injuries hold vast
benefits medically and such advancement will make health services improve beyond measure. It
would save health services a great amount of money, by reducing the number of surgery’s taking
place every day for heart related diseases. However, at the same time it will require medical staff
will extreme technical expertise as it is a complex procedure and acquires perfection. This means the
health services will have to train doctors specifically for this role. This is because a general surgeon
won’t have the correct set of skills that are required for this task. For example, they may know how
to insert the stem cells but they perhaps may not know about the homing of the stem cells to target
tissue.
This method using stem cells is particularly beneficial for old to elderly people. The reason for this is
because statistics suggest heart failure is the leading cause of death and accounts for over “40% of
deaths in those aged 65 and over” [16]. With the help of stem cell treatment, it would mean that
elderly people will live longer and allow them to have a better quality of life. In addition to this,
patients are most likely to be satisfied with stem cell treatment over operations. Mainly because no
transplantations are required which means they won’t have to spend a long time in hospital, they
won’t be on a waiting list for an operation and also they won’t face the dreadful experience of
recovery.
A general problem that we may face is the efficiency of the stem cells. We are unaware how long
they will serve the human body and if there are any long term side effects. For example, if the stem
cells are by chance mutated, and the cells grow uncontrollably and cause negative effect, we will
have to create further solutions that need to be addressed. Therefore, more research needs to be
done into this as it is a major area they need to look into. Nevertheless, we don’t feel that these
issues should hold us back in terms of proceeding with stem cells as it is always the case that there
are always problems in research but later addressed in good time.
Finally, we strongly believe the future of stem cells is promising in respects to medical research and
sooner or later, the advancement will be phenomenon as research and trials are increasingly carried
out. Although the ethical concerns are very pressurising, treatment such as stem cell should be put
into practise and hopefully in the near future, we shall see stem cells playing an important role in
treatment.
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References:
[1]
The definition of embryonic stem cells
http://dictionary.reference.com/browse/embryonic+stem+cell
Figure1: Image of a blastula.
http://worms.zoology.wisc.edu/dd2/echino/cleavage/blastula/assets/dendraster_blast.jpg
[2]
General information on stem cells, published by mediacal news today and written by Peter Crosta
http://www.medicalnewstoday.com/info/stem_cell/
[3]
Epidemiology on myocardial infraction
http://en.wikipedia.org/wiki/Myocardial_infarction
[4]
Induced Pluripotent Stem (iPS) Cells may repair damaged heart
http://www.topnews.in/new-stem-cell-therapy-may-repair-damaged-heart-2191465
[5]
OHSU Evaluating Stem Cell Therapy for Heart Attack Damage
http://www.cellmedicine.com/heart-attack-clinical-trial/
[6]
Ethical issues on stem cell research by united press international
http://www.physorg.com/news66391852.html
[7]
Frequently asked questions on stem cell research by ISSR
http://www.isscr.org/FAQ1.htm
[8]
Potential of stem cells in medicine by Wellcome Trust
http://www.wellcome.ac.uk/About-us/Policy/Spotlight-issues/Human-Fertilisation-and-EmbryologyAct/Stem-cell-basics/WTD040069.htm
[9]
Article on using stem cells to create organs by the life site
http://www.lifesitenews.com/news/breakthrough-new-heart-grown-using-adult-stem-cells/
[10]
Article on using stem cells to create heart valves by the BBC
http://news.bbc.co.uk/1/hi/health/6517645.stm
[11]
Information on genetic engineering from Encyclopedia.com
http://www.encyclopedia.com/topic/genetic_engineering.aspx
[12]
Full description of a myocardial infarction by patient.co.uk
http://www.patient.co.uk/health/Myocardial-Infarction-(Heart-Attack).htm
[13]
Article on a ten year old boy receiving a new trachea from stem cells
http://www.lifesitenews.com/news/archive/ldn/2010/mar/10032303
[14]
History of clonal method stem cells
http://en.wikipedia.org/wiki/Ernest_McCulloch
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[15]
The definition of induced pluripotent stem cells
http://biotech.about.com/od/stemcellresear2/g/ipscells.htm
[16]
Statistics on mortality rate of heart disease related to age
http://www.ncbi.nlm.nih.gov/pubmed/11790921
Figure 2: Image explaining myocardial infraction
http://www.nhlbi.nih.gov/health/health-topics/topics/heartattack/
Figure 3: Image showing how stem cell research is used on mice
http://karthikkn.wordpress.com/2010/07/24/induced-pluripotent-stem-cells-ips-cellsrewindreprogram-and-replace/
Figure 4: Image of induced pluripotent cells
http://topnews.in/files/Stem-Cell-914658.jpg
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