Vidic, 2:00
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INDUCED PLURIPOTENT STEM CELLS AND THEIR POTENTIAL IN
TREATING MYOCARDIAL INFARCTION
Adam VanGorder (ajv34@pitt.edu)
iPSC TECHNOLOGY: AN OVERVIEW
It is a well-known fact that the number one killer in the
United States is heart disease. There are commercial
campaigns on television advertising for heart healthy foods,
as well as promoting activities that could help maintain a fit
and active lifestyle. All of this stems from the fact that
currently, Americans have a great risk of suffering acute
myocardial infarction, or a heart attack, due to our current
style of living. Treatment for these heart attacks currently
only exists in the form of surgery, but there is plenty of
potential for that to change as the world of tissue
engineering and stem cell research develops. A relatively
new form of stem cells, induced pluripotent stem cells
(iPSCs), show great possibility for being the next viable
treatment for infarcted hearts, as they are more ethically
sound and are easily accessible when compared to the
current and other potential techniques. Furthermore, this
iPSC technology is within the codes of ethics that have been
published for all engineers to follow. They are also a
valuable educational tool, to be promoted and used as way to
inform the public of tissue engineering. I would have never
learned about this technology had I not written this paper.
Therefore I would like to see writing projects such as this
incorporated into engineering curricula at other universities
as well. As an aspiring engineer, I want to see this
technology engineered to be more readily available to a
wider set of patients, as cardiovascular disease has been
prevalent and in my personal and family backgrounds.
Induced pluripotent stem cell technology should continue to
be engineered for a more in depth treatment of myocardial
infarction, as its potential is unparalleled by any other
existing treatments.
DETAILS OF iPSC TREATMENT
Treatment using this new technology is exciting, as it
changes the current approach to using tissue engineering to
reanimate effectively dead tissue. This technology is
something worth engineers’ time and effort. The iPSCs are
such a stimulating discovery because they take fully
differentiated adult cells and, using tissue engineering
techniques, drive them backward through the differentiating
process into something that behaves almost exactly like an
embryonic stem cell. This is done by using four cell
conversion factors discovered at a lab in Seoul, South Korea
in 2006 [1]. This discovery is paramount to anything else
regarding stem cell research. Without those factors, iPSC
University of Pittsburgh, Swanson School of Engineering 1
October 9, 2012
technology would not be possible, and society would never
be able to reap their benefits.
Benefits of iPSC Technology
Of the forms of stem cells used in tissue engineering and
regenerative medicine, iPSCs attract a lower amount of
controversy. Generally, engineers and doctors alike
recognize how useful they can be, both ethically and
immunologically. Currently, a fear of using embryonic stem
cells is rejection due to the lineage of the cells being
different from that of the patient. This issue becomes even
more significant when treating myocardial infarctions, as the
tissue rejection would more than likely kill the patient. The
argument for using iPSCs is that they are genetically
identical and epigenetically similar to the patient’s cells.
Therefore, when replacement tissue is engineered, the
likelihood of its rejection is minimal by comparison [2].
Currently, there are so many variables involved with
surgery, such as replacement organ availability. With current
heart transplants, it takes patients years on waiting lists to
find a heart that has the least chance of being rejected, and
most people die before that heart becomes available. Being
able to engineer a treatment for any specific patient’s heart
that has a lower chance of rejection and can be available in a
quicker time is something in which more research dollars
should be invested.
Heart-Specific Treatment
Apart from having the likelihood of rejection low for
treatment of these heart attacks, treatment procedure must be
considered. Tests have been done in mice to see how iPSC
technology can be used to treat acute myocardial infarction
with success. The procedure the team used went as follows:
•
Skeletal muscle cells were obtained and isolated
from a graft off the affected mice.
•
The cells were washed and digested using enzymes
to break them up individually
•
The four conversion factors were added so that the
cells would revert into iPSCs
•
The cells were bathed in culture so that they would
redifferentiate into myocardial cells
•
Myocardial tissue has been engineered and dyed for
observation, and grafts of this new tissue are injected onto
the affected area of the heart.
Adam VanGorder
After the procedure, the mice were observed to have
increased healing of the infarcted tissue, showing successful
treatment with the need for future testing [3]. This
procedure, pending repetition of results, could prove to be
the way human cells are engineered to treat affected hearts.
Using it in any hospital that offers treatment for myocardial
infarction would be the goal for the engineering community,
so that anyone unfortunate enough to suffer a heart attack
could obtain viable treatment.
dictates that the derivation from non-embryonic sources does
not raise additional policy concerns. They are viewed as
more ethical because they do not involve the “death” of an
embryo and are taken with consent from the owner [5].
There has been excessive public debate over the use of
embryonic stem cells and whether their medical potential is
worth the human lives lost. With iPSC technology, tissue
engineers can successfully end the political discussion over
the ethics of this treatment, because more people see no
harm in the derivation of the iPSCs. Although the embryonic
cells are a viable alternative to the iPSCs, the ethical
baggage they carry could inhibit the process of getting a
better treatment for myocardial infarction to the bedside in
due time.
OTHER TREATMENTS AND THEIR
SHORTCOMINGS
The current treatments for myocardial infarction are
functional, but research needs to continue in order to
increase the effectiveness and efficiency for the condition.
Heart surgery works for many patients, but only if the
circumstances are right, including replacement organs on the
donor waiting list. Because there are so many variables, it is
unlikely that open heart surgery can remain the best
treatment of myocardial infarction. Likewise, there are other
cell and tissue engineering treatments being tested,
specifically those involving human-derived embryonic stem
cells. However enticing these treatments may sound, they
carry with them the ethical baggage that embryonic stem
cells have had since their conception. Bearing these ideas in
mind, it becomes clear that the opportunity for therapy by
using iPSCs is the best choice for continued research.
ETHICS AND THEIR EFFECT
As is with many other professions, Engineers must
adhere to a published code of ethics. However, due to the
fact that the field of engineering is so broad, each specific
type of engineers has their own code of ethics that must be
followed. This seems rather obvious, especially when the
engineer is dealing with something so polarizing as stem cell
research and tissue engineering. Both the National Society of
Professional Engineers (NSPE) and the Biomedical
Engineering Society (BES) have published codes of ethics
that are useful to the development of my position.
NSPE Guidelines
Minimally Invasive
As previously mentioned, the standard general code of
ethics for engineers in the United States is published by
NSPE. It acts as an overarching code for all fields of
engineering, so some of its statements are broad, but they
can be applied to specific engineering situations, such as
tissue engineering to cure myocardial infarction. The code
states in as a fundamental canon that “Engineers shall at all
times strive to serve the public interest” with the
accompanying directive “Engineers are encouraged to
extend public knowledge and appreciation of engineering
and its achievements” [6]. Being that heart failure is a huge
cause of death in America, these cellular engineers should
continue to “serve the public interest” by making their
remedy available for the bedside in the near future.
Likewise, making the potential for iPSC technology
common knowledge should be a huge priority for the
cellular engineers involved. However, these engineers must
obey a later canon in the code stating “Engineers shall avoid
all conduct or practice that deceives the public” [6]. When
dealing with the ethical issue of stem cells, it is paramount
that anyone working on the project does not act in a
deceptive manner, as it tarnishes the general good image of
an engineer. Likewise, the public has its trust in the cellular
engineers to make the treatment ethically, and deception
would change that opinion. Acting in a legal and transparent
One of the perks that iPSC technology has over current
myocardial infarction treatments is how it affects the body of
those being treated, as it is a much less invasive procedure.
Current tests with mice involve taking muscular tissue from
the leg to form the pluripotent cells, and simply injecting
them into the affected area. This procedure has a smaller
incisions and subsequent scars as opposed to the current
surgical techniques [4].Making treatment for myocardial
infarction as minimally invasive as possible is key to being
able to treat a larger amount of people. Currently, surgical
procedure involves the opening of the chest cavity by sawing
the sternum. Unfortunately, all patients requiring treatment
cannot recover from such an ordeal. If engineers could find a
way to make the iPSC treatment accessible, the resultant
procedure would be less invasive and thereby more
accessible to a frailer population. In that same vein, iPSC
technology dodges ethical concerns that have been brought
up about tissue engineering research.
Abated Ethical Concerns
Induced pluripotent cells avoid the strict guidelines and
the scrutinizing public eye, as they remove the moral
dilemma of destroying a human embryo. In fact, U.S. Policy
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Adam VanGorder
manner should be the only practice, and the Biomedical
Engineering Society concurs in its code of ethics.
iPSC technology and their use in tissue engineering should
me continued or not. I am happy that I found the program
through research for this writing project, and I am sure other
future engineers would agree.
BES Guidelines
The BES Code of Ethics covers all aspects of the
extensive field of Biomedical Engineering, yet it has no
specific section on tissue engineering. The directives that
most apply state that engineers shall “Comply fully with
legal, ethical, institutional, governmental, and other
applicable research guidelines, respecting the rights of and
exercising the responsibilities to human and animal subjects,
colleagues, the scientific community and the general public”
as well as publishing and presenting research results clearly
and accurately [7]. This clearly reinforces how the NSPE
code should be applied. However, since they are very
similar, I feel that the BES guidelines should create a canon
and set of directives specifically relating to research
involving stem cells, as it is a pressing issue in today’s
society. Currently, the directive is as vague as the NSPE
code, and that leads to a greater chance of misunderstanding.
When dealing with an issue as present as tissue engineering,
policy should be clear and concise.
Writing in Engineering
I have found it extremely beneficial to write this paper
and take a position on a current engineering issue, and I feel
that freshmen at other universities would benefit just as
much. In a chapter of her book on writing in engineering,
Dorothy Windsor states “though this field [Engineering] is
tied to physical reality, it is necessarily accomplished
through language” [9]. Other freshmen could explore a topic
they are truly interested in and find opportunities relating to
it. They could learn all the legal and ethical stipulations of
their topic, and make more informed decisions about how to
approach their engineering education. An example of this in
my life is the program sponsored by PTEI. Other engineers
could find opportunities that are specific for mechanical or
chemical engineering. Overall, this project has been a great
addition to my education, and I am happy to reap its
benefits. However, there is still the question as to why I am
so interested in finding a better treatment for myocardial
infarction.
The Impact of the Codes and my Position
Overall, these codes give good guidance for an engineerto-be interested in developing a position. They helped me
see how the codes of ethics lay a general overview of how
research dealing with iPSC technology and treatment for
myocardial infarction is legal. Furthermore, the codes have
strengthened my position by showing how research should
be continued to serve the public interest of treating heart
attacks. Although I found the BES code to be lacking in
content, it was still useful because of its emphasis and
reiteration of the NSPE code. I would hope that more
engineers would learn about the details of using iPSC
technology and its potentials by continuing their education.
iPSC TREATMENT AND ME
It may seem a little strange why a seemingly healthy 18
year old male would care so passionately about making a
better treatment for something that typically affects people
over 55 years of age. I agree that my interest in the subject is
not paralleled by most people my age in my position, yet I
cannot justify that I care for the wrong reasons. My
worldview and past experiences have shown me how this
issue is something that can affect many people all over the
country at any age, through my family health history, past
medical history, and high school experiences.
THE IMPORTANCE OF iPSCs FOR
FUTURE ENGINEERS
Family Medical History
I have been affected by heart attacks and other forms of
heart disease through my paternal grandfather. Currently, he
is hospitalized, recovering from a second occurrence of
acute myocardial infarction after his first bypass failed. He
cannot undergo surgery again due to his age. . I know that if
a cellular engineering treatment had been available at the
first incidence, he might have had a sustainable recovery. He
is bed ridden now, and as a formerly active man, it pains me
to see him in that state. I hope that one day I may be able to
engineer a way to make cellular treatment possible.
In order to have treatments using iPSC technology be
advanced, education about them must be promoted in all
levels of schooling. Currently, in Pittsburgh, there is a group
that formed to accomplish this feat. The Pittsburgh Tissue
Engineering Initiative (PTEI) provides funding and venues
for programs that teach all ages ranging from kindergarten to
post-doctoral. At least in Pittsburgh, this program should be
encouraged to bring out more interest to iPSC technology.
PTEI provides an opportunity for undergraduate research
internships in the summers [8]. I plan to apply for this
program as it aligns with my interest in the topic of tissue
engineering. These programs are what could help other
future tissue engineers form their own positions on whether
Personal Experiences
I share a similar scare in my own past medical history. I
had my blood pressure taken and it was abnormally high. I
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Adam VanGorder
was admitted to the Cardiology department of Children’s
Hospital and had extensive testing done. Although the
results revealed that my heart was healthy, I was still
nervous that I could suffer heart disease prematurely.
Furthermore, as I advanced through the biological and
medical sciences courses my high school had to offer, I
began to learn about the potentials of both forms of stem
cells. I became infatuated, making them the topic of two
research papers. All of this culminated to when I was in my
Human Anatomy class as a senior in high school. The top
twelve students in the class got to go to Allegheny General
Hospital to see a triple bypass open heart surgery. I was
selected, and I sat there watching as the team of surgeons
helped a sixty year old man overcome an infarcted heart. I
knew that tissue engineering had potential in changing the
abrasive procedure.
Article).
http://www.sciencedirect.com/science/article/pii/S19345909
11003365
[3] R. Ahmed, H. Haider, S. Buccini, et al. (June 24, 2012).
“Reprogramming of skeletal myoblasts for induction of
pluripotency for tumor free cardiomyogenesis in the
infarcted heart.” US National Library of Medicine. (Online
Article).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155953/
[4] R. Ahmed, M. Ashraf, S. Buccini, et al. (June 8, 2011).
“Cardiac Tumorgenic potential of induced pluripotent stem
cells in an immunocompetent hose with myocardial
infartcion.” US National Library of Medicine. (Online
Article).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110348/
[5] T. Caulfield, I. Hyun, K. Kato, et al. (January 2010).
“Stem cell research policy and iPS cells: the field of induced
pluripotent stem cells (iPSCs) will be subject to a wide range
of laws and research ethics policies, many of which exist as
a result of the controversies associated with research on
human embryonic stem cells. Understanding this potentially
complex regulatory environment will help iPSC research
move forward and will inform future policy.” Academic
OneFile.
(Online
Article)
DOI:
http://dx.doi.org/10.1038/NMETH.F.28
[6] “Code of Ethics” National Society of Professional
Engineers.
(Website).
http://www.nspe.org/Ethics/CodeofEthics/index.html
[7] “Biomedical Engineering Society Code of Ethics”
Biomedical
Engineering
Society.
(Website).
http://www.bmes.org/aws/BMES/pt/sp/ethics
[8] “Education” Pittsburgh Tissue Engineering Society.
(Website). http://www.ptei.org/section.php?pageID=8
[9] D. Windsor. (February 1990). “Engineering
Writing/Writing Engineering” College Composition and
Communication.
(Online
Book).
http://www.jstor.org/stable/357883
CONCLUSION: THE ADVANTAGES OF
iPSC TECHNOLOGY AND ITS USES IN
ENGINEERING EDUCATION
Induced Pluripotent Stem Cell technology is a viable
option that cellular engineering should pursue to find
sustainable treatment for infarction of the heart, as they
abate ethical concerns and make for a less invasive and more
accessible treatment. They can be used on a more
widespread range of people, with less chance of being
rejected by the patient, so as to form a viable treatment that
will outlast current surgical endeavors. They can be derived
from any particular human, and have no excess moral
baggage that promotes public outcry and strict public policy.
Likewise, research involving iPSCs is within the established
codes of ethics, and this promotes my position. Furthermore,
writing projects such as this are useful for engineering
curricula as they help aspiring freshmen engineers to learn
more about the field they are pursuing. Specifically, they can
learn of opportunities that could help them plan their future
in their education. Overall, iPSCs form a successful
alternative to the current methods that should be pursued
through research and funding by cellular and tissue
engineers.
ACKNOWLEDGMENTS
I would like to thank my family for supporting me and
getting me to college where I can hope to pursue my
passions. I would also like to thank my high school anatomy
teacher for permitting me to attend the open heart surgery at
Allegheny General Hospital, and for being an inspiration to
me throughout my senior year. I would also like to thank my
Biology I and II teacher for initially sparking my interest in
cellular and tissue engineering. Finally, I would like to thank
the University of Pittsburgh, for accepting me and allowing
me to study in its world renowned facilities.
REFERENCES
[1] A. Panopoulos, S. Ruiz, J. Belmonte. (April 8, 2011).
“iPSCs: Induced Back to Controversy.” Cell Press. (Online
Article).
http://www.sciencedirect.com/science/article/pii/S19345909
11001135
[2] B. Barrilleaux, P. Knoepfler. (August 5, 2011).
“Inducing iPSCs to Escape the Dish.” Cell Press. (Online
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