ENGR0011 VIDIC, 2:00
L06
THE ROLE OF STEM CELLS IN ORGAN REPLACEMENT
Iman Benbourenane (ilb8@pitt.edu)
INTRODUCTION: A NEW LOOK AT STEM
CELL RESEARCH
With the presidential elections closing in upon us, radio
talk shows and cable news outlets are once again dredging
up decades old debates that, given the right conditions, could
turn brother against brother. Questions of religion and ethics
come into play, and stances sternly taken, resulting in
stubbornness on both sides and a clear divide of party lines.
One such topic is embryonic stem cell research. A hot topic,
indeed, but surprisingly little is being said about adult
derived stem cells. Adult derived stem cells provide an
alternative to embryonic stem cell research that allows us to
forgo the politically charged debates on the ethics of stem
cell research. Adult derived stem cells show great promise in
the realm of creating safe, effective treatment for organ
failure. In addition, stem cell research, particularly whole
organ decellularization, allows for generation of organs that
are low risk for rejection and that will provide treatment
options for patients that would otherwise have to wait on a
limited supply of organ donors. Whole organ
decellularization paves the way for lab-made-organs, such as
hearts (which have been successfully reconstructed) and
possibly kidneys. It is an incredibly promising field that that
touches me personally, as a future engineer and hopeful
friend. It deserves funding and attention, not only because
logically it makes sense, but because as engineers we are
ethically obligated to do so, an idea that gives freshmen
engineering students like myself a glimpse into the world of
ethical problem solving.
A CLOSER LOOK AT STEM CELLS
The words “stem cell research” cannot be said without
some strong connotation that goes along with it. Whether
that connotation is positive or negative depends on the
audience. For this reason, it’s a topic that has become taboo
and a subject that everyone has an opinion about, but little
insight as to what it actually is. This is because people most
associate stem cell research with embryonic stem cell
research - a small subset to a large area of study. The debate
on embryonic stem cell research has lead all the way to the
Supreme Court, where a lower court decision (which, if
upheld, would force the cancellation of numerous ongoing
experiments) was overturned in May of 2011 [1]. It’s true
that embryonic stem cells have paved the way to the greater
study of adult stem cells, something that Dr. John B. Gurdon
of the University of Cambridge discovered in 1962, when he
produced living tadpoles from the adult intestinal cells of a
University of Pittsburgh, Swanson School of Engineering 1
9 October 2012
frog. After replacing the nucleus of a frog egg with the
nucleus from the adult cell, the egg was able to reprogram
the adult cell’s nucleus and direct its genes “to switch from
the duties of an intestinal cell to those appropriate to a
developing egg” [2]. The mechanism behind this was not
found until almost half a century later. Working with mice,
recent Nobel Prize winner, Dr. Shinya Yamanaka of Kyoto
University discovered in 2006 that just four specific gene
control agents in the egg could explain the
reprogramming. Furthermore, by simply injecting the four
agents into an adult cell, Dr. Yamanaka showed that he
could “walk the cell back to its primitive, or stem cell,
form”[2]. These cells, known as induced pluripotent stem
cells, could then be made to differentiate into any type of
cell in the body. The implications of this set of studies are
astounding. Firstly, it takes away the ethical debates
associated with embryonic stem cell research and the waste
of human life because the stem cells are derived from adult
cells. In addition, and more importantly, it opens the door to
a seemingly endless line of research in regenerative
medicine, at the forefront of which is organ development specifically, whole organ decellularization.
WHOLE ORGAN DECELLULARIZATION:
AN INNOVATION TO ORGAN FAILURE
TREATMENT
Dr. Doris Taylor of the University of Minnesota
developed the method of whole organ decellularization, a
process by which stem cells are grafted onto the extracellular
matrix of an organ and grow to develop into a fully
functioning organ [3]. Dr. Taylor focused on the heart in her
experiments, starting with a dead mouse heart and removing
the cells. Using detergent, the protein in the heart cells were
denatured, leading to cell lysing, effectively “washing” away
the living cells and leaving only the extracellular matrix.
This matrix, or “scaffolding” as she sometimes refers to it,
can then be used as a template for stem cells to grow on. She
and her team watched in amazement as the cells not only
began to grow around the matrix, but also started contracting
like the cells of a fully functioning heart.
This development has huge implications, because if they
were able to grow a heart in a lab, then theoretically they can
grow any organ, given they have the correct “scaffolding”
and stem cells. Furthermore, this method creates not just
pieces of organs, but entire organs that are identical to the
donor’s organs. This new development could provide
treatment for patients suffering from organ failure and would
Iman Benbourenane
It’s the belief of some researchers that the hype
surrounding stem cell research and organ decellularization is
just that – hype – and will be a repeat of the Human Genome
Project, a project centered around decoding the human
genome that took fifteen years and $3 billion to complete
[7]. Although very interesting, the Human Genome Project
did not produce the results that were promised – a possible
cure to every disease affecting mankind. It amounted to few,
if any, actual cures to diseases and many believe that stem
cell research, too, will amount to almost nothing. So what if
it worked on mice in a few select case studies? Why should
we dedicate our time and energy into what might result in
trivial pursuits?
As a future engineer, this topic matters to me because it
opens the door to a realm of research that, if understood
completely, could serve as a cure-all for a multitude of
diseases [2]. When you have a cell that can differentiate into
any cell at all, endless possibilities are in store [7]. We are at
the forefront of something with great potential, and that
potential lies in the ability of these cells to differentiate into
any possible cell. In the case of whole organ
decellularization, nature has given us the building blocks
(i.e. the extracellular matrix and stems cells) and it is our job
as engineers to manipulate them to benefit society.
Actually, from an ethical viewpoint, one could say it’s
not only the job, but also the duty of engineers to further
research and develop these methods. The very first canon of
the NSPE code of ethics for engineers is to “hold paramount
the safety, health, and welfare of the public” [8]. The
Biomedical Engineering Society further specifies this
statement in their code of ethics by requiring bioengineers to
“… enhance the safety, health, and welfare of the public”
[9]. These ideals are congruent with the intentions of adult
stem cell research. Firstly, by not using embryonic stem
cells, there is no question as to whether human life is being
harmed in the pursuit of knowledge in this new field. The
cells that are used are taken from adults, with their full
consent, and with minimal pain involved. This satisfies the
task of upholding safety, health, and welfare. The real task is
enhancing that safety, health, and welfare. This is done by
using
novel
techniques,
such
as
whole-organ
decellularization, to create alternative methods of already
existing treatments. For example, the current method of
treating heart disease often involves a heart transplant.
Transplants require a donor, and if that donor is not closely
related to the recipient, chances of rejection of the organ are
high. Replacing this risky method with a specially crafted,
healthy version of the organ identical to the recipients
reduces the risk of rejection drastically. Success rates of
surgery would be higher, and thus safety, health, and welfare
of the public would be enhanced.
On a more personal level, I care about stem cell research
because, as the friend of two sickle-cell patients, it gives
hope for possible improvements on already existing
treatments. The two girls, both sisters, were excited to hear
about a bone marrow transplant operation that proved to cure
be preferable to the current method of treatment (i.e. organ
donation) primarily because organs are in short supply [3].
Cardiovascular diseases accounted for 34% of all deaths in
the United States with an associated cost of $503.2 billion in
2010 alone [4]. Over 3,000 people a year are left without any
options for treatment for their various illnesses and diseases
[3]. Whole organ decellularization does require a heart
donation, but it can be from a cadaver, a pig, or any other
mammal that has a heart anatomically similar to a human
heart. This is due to the fact that only the intercellular matrix
is required from an outside source; the actual organ cells
come from the transplant recipient. This leads to the second
reason this method is preferable – less chance of rejection. In
the case of whole organ decellularization, the receiver of the
transplant is also the donor and so the body will be less
likely to target these cells as an outside invading threat and
reject the cells [4]. This eliminates the need for anti-rejection
drugs, which are costly and can have terrible side effects [5].
Still, researchers are skeptical when it comes to this new
advancement, particularly because this method of organ
creation requires a large amount of stem cells [4]. Some find
it difficult to believe that sufficient sources of stem cells
exist to create any organ needed and apply them to benefit
the human body. For example, the kidney is a complex
organ that requires twenty-four different adult cells to
interact to function [6]. The strongest argument against
stems cells and their role in kidney development is made by
Humphreys and colleagues of the Harvard Institute of
Medicine who, when trying to mark the sources of cell
growth, came to the conclusion that most of the cells (that
were thought to be adult stem cells) used to grow the kidney
were not adult stem cells but actually leftover embryonic
cells from development [6].
If the cells were leftovers from development, then using
only adult stem cells in a kidney scaffold may not work.
This finding, if true, would mean the findings from Dr.
Taylor would be limited to only hearts and possibly only
mice hearts when using only adult stem cells. However, Dr.
Scott Reule and Dr. Sandeep Gupta of the University of
Minnesota, using labeling methods of cells, have determined
that the method of cell identification used by Humphreys
and colleagues did not account for stem cells that take on the
phenotypic appearance of embryonic cells. So, the cells
Humphreys dubbed “embryonic leftovers” could actually be
adult stem cells in disguise. Thus, stem cell still remain “a
potential cellular source for kidney regeneration and warrant
further exploration” [6]. These findings open the door to
further research in stem cells and organ reconstruction, even
though limitations still exist, such as definite identification
of stem cell markers.
THE IMPORTANCE OF STEM CELL
RESEARCH: WHO REALLY CARES
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Iman Benbourenane
patients of their sickle cell. They were lucky –
extraordinarily lucky – to have a sibling that was a perfectly
matched donor to both of them. Otherwise, they would have
to rely on an outside source that could result in rejection of
the donated bone marrow and, as they would have to be
immunosuppressed for the operation, ultimately death. The
eldest of the two sisters was operated on first, and it seemed
from the start that her sickle cell was cured. Unfortunately, it
was her heart that failed her, and she passed away from
cardiac arrest at twenty years old. Her sister, only seventeen
and still yet to get the transplant, is faced with the fate of
either dying young from sickle cell, or possibly dying
younger from complications due to the bone marrow
transplant. It’s the promise of adult derived stem cell
research, providing an identical, healthy match to failing
tissue, resulting in no rejection and no need for
immunosuppressants, and whole organ decellularization,
which would provide organs to replace damaged ones, that
gives hope that stories like this become a thing of the past.
Furthermore, if advancements can be made more quickly, it
could be the means of a lucky change of fate for suffering
patients.
as defined by our respective codes of ethics. We were forced
to defend our position with these codes, or if they didn’t
fully support our position, we were given the opportunity to
self-reflect on whether our opinions were the “correct
opinions”. For example, I now see that the method of taking
a stance before doing research is generally not considered
ethically sound. The NSPE code of ethics states that
engineers “…shall be objective… in professional reports”
[8]. Having already taken a stance and researching materials
only in support of my stance, I have taken away some of the
objectivity that an ethical engineering paper should have.
Thus, by providing insight into our own ethics and
comparison to what is expected of us as future engineers,
this assignment provides us with an introduction to ethics
problem solving, which is vital to the field of engineering.
JUST THE BEGINNING: A CONCLUSION
Adult derived stem cells show great promise in the world
of regenerative medicine – so much promise that it
outweighs the risk of a possible dead end. With the help of
whole organ decellularization, safe, rejection-free organs can
be made in lab and replace the current organ donor system of
treatment. The opportunities that lie ahead in this field push
us to question whether or not we are morally obligated to
pursue such research, a question that has freshmen engineers
like myself slowly understanding where we stand on certain
issues and how we must approach such dilemmas. On
reflection, it all sounds a little crazy; really, it is a novel idea
– lab-made organs. It’s like something out of a science
fiction novel. And for now, it’s still fantasy, because to date,
there has been no creation of fully functioning human organs
in lab. We haven’t yet fully entered the world of science
fiction, but this is a good first step.
THE IMPORTANCE OF THIS
ASSIGNMENT: WHO REALLY CARES
My background and research led me to take a stance on
the issue of adult derived stem cells, but really what is the
point of taking a stance on a topic that, as a freshmen
engineering student, I know so little about? As Dr. Bridget
Bero and Dr. Alana Kulhman point out in their paper on
engineering education, although engineering students
generally come into college already possessing black and
white critical thinking skills, things turn grey once the issue
of ethics appears. In the same way we are taught to further
our critical thinking and problem solve, we need practice in
solving ethical problems [10]. An assignment such as this
did two things in aiding our understanding of these grey
areas and strengthening our problem solving skills. Firstly,
by making us pick topics and write our papers before
looking up the ethic codes, we saw where we stood already
on our specified topic. For example, I firmly believed in the
advancement and funding of adult stem cell research. For
me, I went into the paper already knowing I supported it, and
then did research to back up my stance. For other students, it
could have been a stance they had taken only after doing
research. Either way, we were given sufficient time and
resources to make a sound decision on where we stand on a
topic. It gave us a chance to figure out where we stand on
the ethics scale. By understanding where you stand, it makes
comparison to ideals of ethics possible. We are given the
moral compass of the ethical cannons, but they are useless
unless we know our starting point.
Secondly, we were given a chance to compare our stance
to see if our thinking was like that of an “ethical engineer”
REFERENCES
[1] Fox, Maggie. (2011). "Appeals Court Hands Obama a
Stem-Cell Victory." NationalJournal.com. (Online Article).
http://www.nationaljournal.com/healthcare/appeals-courthands-obama-a-stem-cell-victory-20110429 .
[2] Wade, Nicholas. (2012). "Cloning and Stem Cell Work
Earns Nobel." The New York Times. (Online Article).
http://www.nytimes.com/2012/10/09/health/research/cloning
-and-stem-cell-discoveries-earn-nobel-prize-inmedicine.html?_r=1.
[3] “New Heart Built with Stem Cells.” University of
Minnesota Center for Vascular Repair. (2008). (Video).
http://www.youtube.com/watch?v=j9hEFUpTVPA
[4] Iyer, Rohin K., Loraine LY Chiu, Lewis A. Reis, and
Milica
Radisic.
(2011).
"Engineered
Cardiac
Tissues." Current Opinion in Biotechnology. (Online
article).
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Iman Benbourenane
http://www.sciencedirect.com.pitt.idm.oclc.org/science/articl
e/pii/S0958166911000668. p. 706-714
[5] Kisken, Tom. (2011). "Medicare Limits Anti-Rejection
Drugs That Transplant Patients Need."Ventura County Star.
(Online
Article).
http://www.vcstar.com/news/2011/jul/22/medicare-limitsanti-rejection-drugs-that-need/ .
[6] Reule, Scott, and Sandeep Gupta. (2011). "Kidney
Regeneration
and
the
Role
of
Stem
Cells."Organogenesis (Online
Article).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142450/?re
port=abstract. p. 135-139
[7] J. Antonelli. (2012, February 3). Lecture notes. AP
Biology. Peters Township High School.
[8] (July 2007). ”NSPE Code of Ethics for Engineers."
National Society of Professional Engineers. (Web).
<http://www.nspe.org/Ethics/CodeofEthics/index.html>.
[9] (Feb. 2004). "Biomedical Engineering Society Code of
Ethics." Biomedical Engineering Society. (Web).
<http://www.wpi.edu/Images/CMS/Biomedical/BMEethcis.
pdf>.
[10] Bridget Bero and Alana Kulhman. (2011). “Teaching
Ethics to Engineers: Ethical Decision Making Parallels the
Engineering Design Process”. Science & Engineering Ethics.
(Online
article).
http://web.ebscohost.com.pitt.idm.oclc.org/ehost/pdfviewer/
pdfviewer?sid=f8416d79-cd3e-4470-9471f96d8d582cf5%40sessionmgr14&vid=4&hid=12
ACKNOWLEDGMENTS
I would like to thank the lovely people at the writing center
for putting together the longer-than-this-actual-paper writing
requirements for this assignment. I would also like to thank
my mother for making me soup while I wrote this. A special
thanks goes out to Mr. Bisou Bean, my cat, for proofreading.
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