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STEM CELL THERAPY FOR SPINAL CORD INJURIES: ETHICAL DILEMMA
Riddhi Gandhi (rmg61@pitt.edu)
INTRODUCTION: THE ETHICAL
DILEMMAS OF AN ENGINEER
As a stem cell therapy research team member for the
Pittsburgh Spinal Cord Injury Center, I have always thought
that my work is rewarding and meaningful. After all, the
research we are doing can someday turn into a cure for treating
spinal cord injuries (SCI) and give hope to millions of people
worldwide who currently are disabled to some extent due to a
spinal cord injury. It is estimated that almost 55% of SCI’s are
at the cervical level causing quadriplegia that results in loss of
motor and sensory function in the arms, torso and legs [1].
Approximately 10% of these patients will die in the first year
following injury while the expected lifespan of the remaining
patients is about 10-15 years after injury [1]. Considering that
the average age of people with SCI is between 18-25 years,
these statistics seem even more disturbing [2]. Over the past
three years, my team and I have made some promising
breakthroughs in administering stem cell derived therapies on
rat models with spinal cord diseases or injuries. Transplanting
human neural stem cells in rats with lumbar injuries have
shown great improvement in motor and sensory functions
along with reduced spasticity [3]. However, some experiments
done on rat models with thoracic spine injuries have shown
mixed results based on which, we have concluded that the
sooner the treatment starts after injury the better the chances of
recovery.
Recently, we have been approached by an international
organization to administer such therapies on humans with
thoracic spinal cord injuries. While the prospect of treating
humans with SCI is very appealing; our team is sort of divided
50/50 in whether or not to accept this proposal. On one hand,
it is our chance to do what we all have worked so hard for; to
treat patients with SCI and improve the quality of their lives.
Also, if we are successful, it would bring us international fame.
The organization has also promised to fund us for buying
additional equipment that can help us enormously in
continuing our research efforts. On the other hand there are
several ethical concerns that need to be addressed before we
can make a decision. As a key member of this research team, I
have been asked by our team leader Dr. Joe Kramer to put
together a paper that explains why I feel that we should not
accept the offer at this point in time.
In ordinary circumstances, this would have seemed like a
challenging task given the perspectives of some team
members. However, my decision is impartial and is based on
the ethical training that I have had over the years as part of my
engineering curriculum, and the many ethical seminars I have
attended over the last decade. As stated by the U.S. Bureau of
Labor Statistics (BLS) engineers are groomed to “analyze and
University of Pittsburgh, Swanson School of Engineering 1
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design solutions to problems in biology and medicine, with the
goal of improving the quality and effectiveness of patient care”
[4]. In order for me to effectively communicate my viewpoints
to my team I will first outline what I feel is my role and my
responsibility as an engineer. Next I will discuss the
pathophysiological processes that occur when there is a SCI
and then list the ethical concerns that warrant the need for more
clinical trials to eradicate the risk factors associated with stem
cell therapy and evaluate those concerns against different
engineering codes of ethics. Finally, as an engineer it is also
my job to come up with creative ways of problem solving. I
will therefore, also present a solution that I feel will help us
address this situation effectively. I strongly believe that stem
cell therapy holds great promise in treating people with SCI,
and once we can ensure that the treatment is safe and effective
and will not cause any major ethical concerns, we should be
able to go ahead with such clinical trials.
THE ROLE AND RESPONSIBILITIES OF AN
ENGINEER
Engineers possess a high level of technical knowledge that
can become dangerous for society if it is not subjected to an
overall code of ethical conduct [6]. Ethical principles have
been discussed for centuries as people reflected on why they
did what they did and what were the consequences of their
actions [6]. Thus, many reliable codes of ethics have been
formulated including some specialized codes designed
exclusively for engineering fields and it is every engineer’s
responsibility to not just be aware of these codes but to adhere
to them as well.
Challenges arise when at times the lack of clarity in the
terminology of these codes creates an ethical dilemma for the
engineers. There are times when an engineer is required to
evaluate a particular situation in the light of tradeoffs such as
the risks versus the benefits or the safety of a procedure or
product versus its financial impact [6]. In this case, I evaluated
the situation against the various ethical codes that I have
referred in the past and have come to rely on. For instance, one
of the code of ethics of the National Society of Professional
Engineers (NSPE) states that “Engineers, in the fulfillment of
their duties, shall hold paramount the safety, health and
welfare of the public” [7]. Considering this fundamental
canon, I first asked myself if it is ethical to administer stem cell
therapy to humans with SCI, when the experimental data is still
in its early developmental stage. Individuals with SCI are a
particularly vulnerable group of people who have an intense
desire to find a cure for their problem. Is it ethical to treat them
when we don’t have sufficient scientific controls and analysis
of the results? [8]. The safety of stem cell therapy is still being
Riddhi Gandhi
evaluated in terms of its harvesting process, purity of the cell
population, immunogenicity and tumorigenicity [8]. Another
concern is regarding the effectiveness of stem cell therapy for
SCI if administered without any other supporting treatments.
For instance, I believe that stem cell therapy will be most
successful when combined with other strategies such as
neuroprotection that can counter the second occurrence in SCI
[8]. In order to understand these complex issues better, let’s
take a look at the pathophysiology of spinal cord injury.
has been too much controversy surrounding stem cell therapy.
A decade ago, the big focus was embryonic stem cells. On one
hand there were religious leaders and other pro-life activists
arguing that using embryos for clinical trials of stem cell
therapy is equivalent to destroying life. On the other hand, we
had the media and the politicians blowing the topic out of
proportion for their own selfish interests. Even the US
Government had at one point in time withdrawn funding for
stem cell research [13]. Much of the concerns were based on
fundamental issues such as the rights and legal status of an
embryo. With the success of induced pluripotent stem cells,
embryonic stem cells took a back seat as scientists were able
to replace embryonic stem cells with induced pluripotent stem
cells in their research efforts. However, critics argued that
induced pluripotent stem cell based research and therapeutic
cloning could result in misuse of the power of this technology.
With government intervention, some of these concerns have
now been addressed.
The risk factors that are of great concern to me in
administering stem cell therapy to humans are: the variations
in differentiation status, the route of administration, the
intended location, irreversibility of treatment and inadequate
data on long-term survival of engrafted cells [12]. “Directly
injecting cells percutaneously creates many new concerns:
cerebrospinal fluid leak associated with multiple punctures of
the dura mater; uncontrolled hemorrhage from damaged spinal
cord blood vessels; inaccurate targeting due to displacement of
the spinal cord from cannula insertion; and a limited range of
injection sites due to obstruction from the vertebral column”
[11]. Some studies have also shown tumor formation after
induced pluripotent cells were injected in mice [9]. While
clinical trials have shown great success in treating animal
models, there is still lack of qualitative and quantitative data
that can prove its safety and effectiveness. Globally, there are
some disturbing reports of complications in patients treated
with stem cell therapy. A young boy with a rare degenerative
neural condition, who had been treated with fetal neural stem
cells in Russia, later developed a brain tumor and doctors have
linked the tumor to the stem cells used for treatment [14].
When scientists analyzed the cells that caused the tumor, they
found that the tumor forming cells were donated cells that had
come from two embryos aborted between 8-14 weeks. This
emphasizes the risks that can arise from donated cells. In
China, several individuals with spinal cord injuries who had
received stem cell therapy developed meningitis after
treatment [14]. Such statistics cloud the great promise of
regenerative medicine. Researchers need to evaluate the
intrinsic risk factors wherein the origin of the cells, its
differentiation status and its long-term viability need to be
analyzed before treatment or it can pose potential risks such as
rejection of cells, toxicity and tumor formation [12].
THE PATHOPHISIOLOGY OF SPINAL
CORD INJURY
Spinal cord injury is a two-stage phenomenon. The first
stage is the actual physical injury while the second stage is the
molecular and cellular changes that occur naturally as the body
responds to the injury [1]. While these changes are good to
some extent as they help seal the site of injury to prevent
further damage, they are also detrimental to the SCI recovery
process. When a spinal cord injury occurs, the rarely dividing
ependymal cells are activated and within three days after injury
these newly formed astrocytic cells migrate towards the injury
site and assist with the formation of the glial scar [9]. The
secretion of inhibitory molecules causes the formation of the
glial scar which unfortunately also has some detrimental
effects as it acts as a physical and chemical barrier to
regeneration [10]. The fibroblast like stromal cells that make
up the core of the glial scar help seal the lesion and help retain
tissue integrity. However, the loss of oligodendrocytes causes
the intact axons to malfunction and degenerate over time [9].
Thus the neuron connections between the brain and the spinal
cord are disrupted. In most cases of severe injury, chances of
spinal recovery are very minimal.
Some recent studies have shown that the radial glia cells
can be induced to migrate into grafted channels to form a
pathway that can guide regenerating axons to the site of injury
to help with recovery [9]. A trial for chronic SCI using
magnetically labeled autologous bone marrow cells that were
injected in the patient’s body via intrathecal infusion and
monitored by magnetic resonance imaging (MRI) showed that
the cells did migrate to the site of injury [11]. However, such
treatment options also have inherent risks like puncturing of
the spine that can cause the cerebral fluid to leak. Given this
sensitivity of the spine and its very complex structure, it is very
important to discuss in detail the various risk factors associated
with stem cell therapy.
RISK FACTORS AND ETHICAL CONCERNS
WHEN USING STEM CELL THERAPY TO
TREAT SCI
I wholeheartedly agree that regenerative medicine has great
potential. After all, I have invested many years in this field
doing research with the hope that someday SCI related
disabilities will become the thing of the past. However, there
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Riddhi Gandhi
Even extrinsic factors such as lack of donor history, storage
conditions of cells and transport conditions can result in
disease transmission and cell line contamination whereas
injection of concentrated stem cells into tissue may have
unwanted effects such as development of pulmonary emboli
[12]. These risk factors pose many ethical concerns and as an
engineer who must hold paramount the safety and welfare of
the public, I cannot see myself agreeing to the proposal just
yet. According to the Biomedical Engineering Society
(BMES), engineers have professional obligations, health care
obligations and research obligations that they are required to
fulfill [16]. One of the obligations is to “consider the larger
consequences of their work in regard to cost, availability, and
delivery of health care” [16]. At this point, I feel that the larger
consequence of the given situation is that it can potentially put
a needy population at greater risk. In addition to that, failure of
clinical trials like this can subject the already controversial
topic of stem cell therapy to further criticism and if further
research in this area is not encouraged, we may be giving up
on an otherwise promising way to treat many conditions that
we currently do not have effective cures for. Stem cell therapy
not only has potential to treat spinal cord injuries but also
degenerative disc diseases that is the fifth most common
reason for physician visits [18].
Therefore, it is to our advantage to prevent further criticism
over such promising therapy or else funding for further
research will quickly dry up. For instance, consider the time
when there was great enthusiasm around adrenal and fetal
neural transplantation for Parkinson’s disease that had seemed
very promising at first. However, the lack of effectiveness, the
ethical concerns surrounding it and the side effects all made
this a rather unpopular form of treatment for the desperate and
eventually disappointed people [8]. Currently, only a handful
of very specialized clinics offer this therapy to a select few
patients.
arrhythmias (irregular heartbeats) in some patients.
Researchers have since linked stem cell type, the route of
administration and incomplete differentiation of the donated
cells to these occurrences of arrhythmias [12]. I agree that such
cases are rare but they do happen and this poses ethical
concerns over the use of this therapy. Also, we need to
establish a consensus on what the acceptable standards are for
post-treatment evaluations. When will we be able to gather
sufficient reliable data to ensure the safety of this therapy? To
some extent, it is a chicken and egg scenario. We cannot gather
enough data, if we do not carry out the clinical trial. And yet,
we cannot ethically carry out more trials unless its safety and
effectiveness has been adequately measured. I discussed this
dilemma with my professor and mentor Dr. Narayan of
Middlesex County College, who had first introduced me to the
concept of regenerative medicine. She has been a strong
guiding force in my life and over the years has helped me
resolve many professional conflicts. Dr. Narayan also agreed
to my viewpoints. However, she too suggested that since this
therapy holds great promise and since we have already made
great strides in this research, instead of rejecting the proposal,
we should perhaps postpone accepting it until we can make
some changes that address the key ethical concerns.
Based on all the sources that I consulted to resolve this
ethical dilemma, I propose that we expand our own laboratory
facilities so that we can develop induced pluripotent stem cells
within our laboratory and that whenever possible, these cells
must be derived from the adult stem cells of the patient
themselves. This will reduce the rejection rate and also
eradicate potential risks of donor related diseases. By limiting
the operations to our own lab facilities we also eliminate other
extrinsic risks related to conditions the cells are subject to
during storage and transportation. We also need to come up
with an effective methodology of administering the therapy.
The site of injection has to be precisely targeted so that there
are no complications of puncturing the spine in the wrong area.
Also, research has shown that the migration rate of adult
mesenchymal stem cells beyond the injection site is limited.
Therefore, alternative ways to administer therapy needs to be
explored so as to maximize benefit [1]. Finally, I suggest that
our organization appoint an internal “Ethics Committee” that
will be responsible to gauge the safety of the procedure before
we can begin this phase 1 trial. I agree that every clinical trial
has some amount of risks associated with them, but if we can
make small changes that can help combat the bigger risk
factors, we will be able to ethically proceed in our mission of
finding a cure for individuals with SCI and help improve the
lives of millions of individuals around the world.
CONCLUSION: A NEED TO CONDUCT
MORE RESEARCH BEFORE TREATING
HUMANS WITH SCI
After evaluating all the risk factors, I believe that
researchers need to be mindful of the several ethical issues
related to this innovative treatment option. I know that some
members of my team want to go ahead and accept this proposal
now. I also know that they are well-intentioned and competent
individuals who strongly believe in the success of this
procedure. However, I feel that at this time when this research
is still in its preliminary stage, it would be ethically incorrect
to subject a vulnerable population to this treatment [17]. What
if we do not succeed? Is it right to give these individuals false
hope and even worse, risk that their condition can even further
deteriorate if they develop complications after treatment? For
instance, a clinical trial where stem cell therapy was used to
treat patients with myocardial infarction (heart attack) caused
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Riddhi Gandhi
(Online
Article)
http://stemcellres.com/content/pdf/scrt115.pdf
[12] C.A. Herberts, M. Kwa, H. Hermsen (2011) “Risk factors
in the development of stem cell therapy” Journal of
Translational
Medicine
(Online
Article)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070641/
[13] L. S. Friedman (2011) Writing the Critical Essay: Stem
Cell Research, An Opposing Viewpoints Guide MI:
Greenhaven Press. (Print Book) pp 24-39
[14] D. Jones, MD (2013) “Bioethics in Practice: A Quarterly
Column About Medical Ethics: Stem Cell Ethics” The Ochsner
Journal
(Online
Article)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603193/
[15] K. Hug and G. Hermeren; Editors (2011) Translational
Stem Cell Research: Issues Beyond the Debate on the Moral
Status of the Human Embryo NY: Humane Press (Print Book)
pp 403-420
[16] “Biomedical Engineering Society Code of Ethics” (2004)
Biomedical
Engineering
Society
(Online
Article)
http://bmes.org/files/2004%20Approved%20%20Code%20of
%20Ethics(2).pdf
[17] J. Kimmelman and A.J. London (2011) “Predicting
Harms and Benefits in Translational Trials: Ethics, Evidence,
and Uncertainty” PLoS Medicine (Online Article)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050916/
[18] D. Drazin, J. Rosner, P. Avalos and F. Acosta (2012)
“Stem Cell Therapy for Degenerative Disc Disease” Advances
in
Orthopaedics
(Online
Article)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347696/
REFERENCES
[1] R. Vawda, J. Wilcox and M.G. Fehlings (2012) “ Current
stem cell treatments for spinal cord injury” Indian Journal of
Orthopaedics
(Online
Article)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270592/?rep
ort=printable
[2] “Spinal Cord Injury Facts and Figures at a Glance” (2013)
National Spinal Cord Injury Statistical Center, Birmingham,
Alabama
(Online
Article)
https://www.nscisc.uab.edu/PublicDocuments/fact_figures_d
ocs/Facts%202013.pdf
[3] A. Rebollo (2013) “Stem Cell Injections Improve Spinal
Injuries in Rats” University of California San Diego (Online
Article) http://health.ucsd.edu/news/releases/Pages/2013-0528-stem-cell-spinal-graft.aspx
[4] “Biomedical Engineers” (2012-13) Occupational Outlook
Handbook, U.S. Bureau of Labor Statistics, U.S. Department
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Labor
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http://www.bls.gov/ooh/architecture-andengineering/print/biomedical-engineers.htm
[5] P. Kosky, R.T. Balmer, W.D. Keat and G. Wise (2013)
Exploring Engineering: An Introduction to Engineering and
Design Third Edition MA: Academic Press. (Print Book) pp 314
[6] W. Loendorf (2013) “Engineering and Personal Ethics: For
use on and off the job” (Online Powerpoint Presentation)
http://www.powershow.com/view/3d09daZWZkN/Engineering_and_Personal_Ethics_powerpoint_ppt_
presentation
[7] “NSPE Code of Ethics for Engineers – Fundamental
Canons” (2007) National Society of Professional Engineers
Publication
#1102
(Online
Article)
http://www.nspe.org/resources/pdfs/Ethics/CodeofEthics/Cod
e-2007-July.pdf
[8] J.V.Rosenfeld, P.Bandopadhyay, T. Goldschlager,
D.J.Brown (2010) “The Ethics of the Treatment of Spinal Cord
Injury: Stem Cell Transplants, Motor Neuroprosthetics, and
Social Equity” Topics in Spinal Cord Injury Rehabilitation
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846325/
[9] H. Sabelstrom, M. Stenudd, J. Frisen (2013) “Neural Stem
Cells in the adult spinal cord” Experimental Neurology
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Article)
http://dx.doi.org/10.1016/j.expneurol.2013.01.026
[10] A.J. Mothe and C.H. Tator (2012) “Advances in stem cell
therapy for spinal cord injury” The Journal of Clinical
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(Online
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http://www.jci.org/articles/view/64124
[11] E.M. Donnelly, J. Lammana, N.M. Boulis (2012). “Stem
cell therapy for the spinal cord” Stem Cell Research & Therapy
ADDITIONAL SOURCES
S.P. Heys and J. Kimmelman (2013) “Ethics, Error, and Initial
Trials of Efficacy” Science Translational Medicine (Online
Article)
http://stm.sciencemag.org/content/5/184/184fs16.full?ijkey=z
.4dnJsvjsYeQ&keytype=ref&siteid=scitransmed
ACKNOWLEDGMENTS
I would like to thank Ms. Judith Brink, the librarian at
Bevier Library, who helped me find the online resources for
this assignment and Mr. Dan McMillan for his helpful
comments and ongoing support during this writing process. I
also want to thank Dr. Narayan of Middlesex County College,
New Jersey, who first introduced me to regenerative medicine.
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