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ddn Editorial Roundtable: Ethics and stem cell research
August 2011
EDIT CONNECT
SHARING OPTIONS:
Since the first derivation of embryonic stem cells (ESCs) in mice in
1981 and subsequent discoveries involving human
ESCs (hESCs), this form of stem
cell research has been the subject of much ethical, moral and social controversy.
In fact, in an attempt to resolve
some of these concerns and ensure that
important medical discoveries continue to progress, the last three American
presidents and their government
colleagues have set policies impacting ESC
research in various ways. Where ambiguity exists in this debate on a federal
level, some states have drawn a
clear line in the sand about which forms of
stem cell research may be conducted and publicly funded. And while legislators
may lack the appetite to
tackle this debate, plaintiffs in lawsuits filed at
every court level are seeking the last word on the use of embryos in stem cell
research.
In this, the second installment of our three-part series on trends in
stem cell research, we brought together
three individuals engaged in various
forms of stem cell-related research to discuss some of the controversies
surrounding this burgeoning scientific
field. Their views on the use of
different types of stem cells, the promise they hold for patients and some of
the public concerns about them are
diverse and insightful.
Participating in this roundtable discussion were the following
researchers:
![]() ![]() ![]() ddn: Describe your current stem-cell related work.
Deisher: My work is
focused on non-invasive small molecules and biologics to block
unintended stem
cell sequestration, enabling significantly increased stem cell delivery and
retention in target organs.
McErlane: I had a keen
interest in the therapeutic potential of stem cells from a targeting
perspective during my post-doctorate work with cytochrome P450-1B1 prodrugs,
which was further developed during my project work with Genzyme working
on a
cell therapy initiative in new territories. I am delighted to be able to extend
and build on this work at Sistemic, where by aiding the
development of safe and
effective cells for therapy, I believe the field can really begin to fulfill
its immense potential. Recently, I was requested
to write an editorial review
for this quarter's European
Biopharmaceutical Review focusing on the state of the cell therapy
industry, and
Sistemic's technology at the International
Society for Stem Cell
Research in Toronto and the Stem Cell
Europe meeting in Edinburgh this year.
Pittenger: We are
trying to improve the
engraftment of stem cells, most notably in the infarcted
heart. While the MSCs have multiple abilities that may be beneficial in tissue
repair, the low
early engraftment limits their potential. Any improvements we
find for the engraftment of MSCs will likely be useful for other types of stem
cells as
well.
ddn: What types of
cell lines do you use and why? How
do you obtain them?
Deisher: We tend not
to work with stem cell lines, although we do periodically work with culture-expanded
mixed stem cell
populations. We predominantly work with primary mononuclear
cell fractions containing multiple stem cell types from bone marrow and whole
blood, or
with mixed stem cell populations including HSCs, MSCs and VSELs
positively selected from mononuclear fractions from bone marrow and whole
blood.
Additionally, we work with culture-expanded mixed stem cells derived
from mononuclear cell fractions from bone marrow and whole blood. We typically
obtain fresh cells for each experiment since the types of mixed populations of
adult stem cells described above are the stem cells that are bringing the
most
benefit to patients. This does necessitate long experimental days from start to
finish, as the isolation procedures require four to six hours of
work.
McErlane: The SistemQC
approach we have developed is applicable to all cell
types, so we work on
somatic cells and also stem cells. Within stem cells, we have worked with
iPSCs, hESCs and of course adult stem cells. We obtain
cells from our collaborators
and/or clients. Our collaborators and clients are a mixture of companies and
academic institutions that are focused on
using stem cells to develop
therapeutics or to develop biologically relevant cell line models for drug
discovery and development screening.
Pittenger: We isolate
mesenchymal stem cells (MSCs) from bone marrow. They can be isolated by a
minimally invasive procedure without sacrificing other healthy tissues, and
their expansion in the lab yields millions to billions of stem cells.
These
MSCs have very reproducible characteristics and differentiate to multiple
lineages. We harvest bone marrow from rats, pigs or sheep, and we can
order the
human bone marrow from commercial sources.
ddn: What are the advantages of using adult stem
cells? Embryonic stem cells? Induced pluripotent stem cells?
Deisher: The
advantages of using adult stem cells to treat
patients, particularly using
mixed stem cell populations within mononuclear cell fractions, are: 1)
demonstrated effectiveness; 2) availability; 3)
patient specificity; 4) lack of
immune rejection; 5) affordability; and 6) safety.
Pluripotent stem cells, both embryonic and
induced, provide advantages
for basic research in the laboratory since they grow irrepressibly and provide
ready source material that enhances
scientific convenience.
Additionally, induced pluripotent stem cells provide the opportunity to
study disease using patient-
specific stem cell lines.
McErlane: The
advantage of using embryonic stem cells over
adult stem cells is their level of
ability to differentiate into all cell types of the body due to their
pluripotency. Adult stem cells are limited to
differentiating into different
cell types of their tissue of origin. Another advantage of using embryonic stem
cells is that they can be grown easily
in culture, in comparison to adult stem
cells, which are rare in tissues, making the isolation and expansion of these
cells challenging. Since it is
likely that large numbers of cells will be
required to produce cell therapies for patients, embryonic stem cells have the
advantage due to their growth
and volume characteristics.
An advantage of using adult stem cells over embryonic stem cells lies
in
the fact that there is a question of whether embryonic stem cells, once
implanted, will cause rejection. Adult stem cells are thought to be less likely
to cause rejection. For example, a patient supplying his or her own adult stem
cells can be expanded in the laboratory and then re-introduced back to
the
patient, where the new cells would be unlikely to be rejected by the immune
system as they originated in the patient. Not being at risk of immune
rejection
is a great advantage, as it abolishes the need for taking immunosuppressive
drugs over the lifetime of the patient.
iPSCs and ESCs are very similar in many respects, and the comparison
between adult and ESCs hold true for iPSCs also.
Pittenger: Adult
mesenchymal stem cells have few ethical arguments against their use.
They can
be easily grown ex vivo,
characterized in many ways and formulated for use in tissue repair therapies or
limiting immune
responses. They are normally found in the adult tissues that
need repair, but in insufficient numbers. They have now been safely implanted
in more than
1,500 patients. Although embryonic stem cells and iPSCs may provide
stem cells for more cell types than MSCs, both form teratomas in vivo, and
this problem needs to be
carefully solved before they are likely to be safe for clinical therapies.
ddn: Are induced pluripotent stem
cells a good
alternative to human embryonic stem cells? Why or why not?
Deisher: Induced
pluripotent stem cells are a superior choice over embryonic stem cells for
studying disease development since they can be disease-specific.
McErlane: An advantage
of iPSCs over ESCs is the fact that since the cells will be a near-identical
match to the cell donor,
rejection by the immune system is thought to be
unlikely. A similar potential disadvantage of both iPSCs and ESCs is the fact
that both cell lines have
the ability to produce teratomas—unlike adult stem
cells—and this is of major concern to the people working in the field, as at
the end of the day, we
all want to bring only effective and safe treatments to
patients. The iPSC strategy creates pluripotent stem cells that, together with
studies of other
types of pluripotent stem cells, will help researchers learn
how to reprogram cells to repair damaged tissues in the human body.
Pittenger: The iPSCs
are a good alternative to ESCs and have many properties of ESCs,
but producing
them efficiently is still difficult. The iPSCs can be made without the need for
integrating vectors, but the process is not optimal. The
iPSCs may have
limitations on their differentiation owing to their tissue of origin or the
adult nature of the starting cells.
ddn: Scientifically speaking, what are the
disadvantages or risks of using each of these types of cells?
Deisher: Pluripotent
stem cells, including
embryonic and induced pluripotent stem cells, form tumors
by their very nature, and this tumor formation cannot be eliminated or removed
completely
either by cell culture differentiation or manufacturing techniques.
Pluripotent stem cells also present economic risks as the price of these types
of
treatments, when they have been publicly estimated, are placed at just under
$500,000 (according to a press release by Thomas Okarma, CEO of Geron Corp.).
Additionally, embryonic
stem cell therapies present issues of immune rejection.
Drugs to counter immune rejection themselves pose risks of diabetes,
hypertension and
osteoporosis.
In the United States, horses, dogs, cats and donkeys are being treated
with adult stem cell treatments. For instance, instead of a
$12,000 knee or hip
replacement, dogs can receive $1,800 stem cell therapy with equivalent results.
If one asked a veterinarian why they are not
treating their animal patients
with embryonic stem cells, they would tell you that embryonic stem cells are
prohibitively expensive, and present
dangers of tumor formation and immune
rejection.
McErlane: There are
some major
differences between iPSCs and ESCs worth noting. The genetic
manipulation at present that is required to produce iPSCs, and the long-term
consequences
of this manipulation after transplantation to the patient, is a
big unanswered question of the moment. In addition, there are queries around
iPSCs
maintaining the genetic memory of their origin, and the long-term
consequences have also yet to be understood.
Pittenger: Today, I
would say that for adult stem cells such as MSCs, the largest
disadvantage is
the limited engraftment and their limited differentiation potential to certain
lineages. For ESCs and iPSCs, the major disadvantage is
the formation of teratomas,
that is, the lack of control over their growth and differentiation.
ddn: What is your position on some of the current
moral
and ethical questions surrounding embryonic stem cell research? Has this
debate impacted your work? If so, how?
Deisher: Science
should never be removed from ethical
and moral oversight. History has taught us
this too many times for us to now believe that science is above morals and
ethics. The Sherley vs.
Sebelius
lawsuit, of which I am a plaintiff, asks the courts to uphold the laws of
Congress and the intent of Congress in passing the Dickey-
Wicker Amendment each
year since 1996.
McErlane: I personally
believe that there
are misconceptions surrounding the moral and ethical
questions that surround hESC research, especially in the area that not all ESC
research causes the
destruction of embryos. In fact, there any many other
research techniques available now to produce ESCs that do not harm or destroy
the embryo, such as
single cells from a blastocyst, dead embryos, non-embryo sources
of stem cells created using altered nuclear transfer, parthenogenetic stem
cells and
germ-cell-derived stem cells. It is my belief that it is our job as
scientists to educate the wider public on the alternate sources of ESCs, which
I
believe to some degree would dispel some of the currently popular beliefs
held in this area.
Pittenger: I am not
insensitive to the issues, but to me, the fertilized egg is not an individual,
and in vivo, many
embryos do not
implant or develop. To me, the ethical and moral questions about undeveloped
human embryos pale in comparison to the moral questions of
life and death of
children and adults everywhere. I believe any embryos that were created for in-vitro fertilization and are in
freezers but
unused eventually will be destroyed by letting them thaw and then
discarding them. I would rather see this resource used for helping others.
ddn: How have these moral and ethical concerns
impacted the
overall progress of stem cell research?
Deisher: Adult stem
cell clinical progress has been impeded in the United States because the
polarizing moral debates have
hijacked the discussion away from the true
interests of patients. Objective analysis, regardless of one's views about the
stage at which human life
deserves protection, concludes that adult stem cells
are the preferred stem cell to treat patients. Effectiveness, safety,
availability and
affordability criteria all place adult stem cells as the
preferred stem cell therapy.
McErlane: These public
concerns have impacted the overall progress of stem cell research in some
countries more than others,
and at the end of the day, it goes back to us
educating the public about the types of cells we use, how they are generated
and the potential of these
types of treatments to improve and even cure patient
diseases, as well as lessening the economic burden of healthcare on our
economies.
Pittenger: Certainly,
this topic has been debated broadly, and could be debated even if stem cells
were
very successful at repairing tissue and relieving pain and suffering. I think
there are technical hurdles that have been difficult to overcome
that have
delayed progress more than the moral debate, but one never knows if the next
dollar spent on the next experiment can solve the problem, and
certainly there
was a multi-year ban on ESC research.
ddn: How can those who are pro-embryonic stem cell
research and anti-
embryonic stem cell research find common ground? What
discussions must we have?
Deisher: We can find
common ground if we place the true interests of patients first and if we have
full disclosure about present
and future research intentions. If the real goal
of embryonic stem cell research is human cloning, and this is not honestly
disclosed, then many
discussions are seriously hampered.
McErlane: It is all
about basic
communication, where everyone understands at a basic level the
issues we are discussing. Perhaps as scientists, we need to become more adept
at
translating the theories in our laboratories out to the general public so
there is a better understanding of what we do without misconceptions.
Pittenger: The moral
and ethical issues may not be easily agreed upon, but there are
many scientific
questions that can be posed equally for adult and embryonic stem cells. Some of
these questions are the practical issues, such as can
the cells be grown to
large numbers in reproducible manner to provide a well-characterized reliable
source for tissue regeneration needs?
ddn: What should the government's role be in funding
stem cell research (in any form), or legislating and regulating what types of
stem cell research can be conducted?
Deisher: Stem
cell
research that involves the destruction of human embryos or that promotes human
therapeutic or reproductive cloning is justifiably regulated by our
elected
officials, locally and federally, and by open public debate and votes of the
people.
Pittenger: The
government is deeply involved in healthcare and therapeutics at all levels:
research, development, safety
assessment, regulatory aspects, efficacy
assessment and recommended best practice. The government should assure the
safety of potential cell
therapeutic products, and therefore needs to fund
research at many different levels. Unfortunately, the government often operates
as a non-scientific,
political body that reflects views of politicians, rather
than scientists and doctors trying to improve healthcare.
ddn: To what extent has the controversy associated
with human embryonic stem cell research impacted the public's understanding
of
science? How can we improve this understanding?
Deisher: As Dr. Art
Caplan, an embryonic stem cell proponent, stated in December 2010, "Embryonic
stem cell research
was
completely overhyped, in terms of its promise. And people knew it at the
time. I tried to say so myself at different times myself, even though I support
embryonic stem cell
research. But this notion that people would be out of their wheelchairs within
a year if we could just get embryonic stemcell
research funded was just ludicrous. Just simply silly. Yes, those saying it had
to know it at the time. The scientists had to have known that."
The public's understanding of science might be improved by clearer and
more
truthful statements from scientists, and by less biased coverage of
science by the media, which at times reaches the level of untruthful reporting.
Pittenger: The public's
interest in science is very
important to assure funding of research and
development. Controversy in science leads to more available information on both
sides of the arguments, and
individuals will then need to become better
informed and make their own decisions. Clear, concise information from reliable
sources needs to be
available.
ddn: In your view, what is the biggest misconception
about stem cell
research, and what can be done to change that misconception?
Deisher: The biggest
misconception is that pluripotent stem cells (which includes both embryonic and
induced pluripotent stem
cells) are the magic potion for patient therapy. Stem
cell treatments to date that have helped patients have all used adult stem
cells, predominantly
mononuclear stem cell fractions taken from various sources
within the patients themselves. Pluripotent stem cells are fraught with safety
problems and
are years behind adult stem cells, and they may never help
patients because of their safety problems.
This misconception will be changed when media and other agents that
disseminate stem cell news correctly and truthfully
identify the source of the
positive stem cell results they are reporting as adult stem cells. Unfortunately, when the news covers stem cell
success
stories, the word adult is
commonly dropped, leading the public to think that the progress was made with
embryonic stem cells—when in fact, embryonic
stem cells have not helped anyone.
Accurate reporting is not too much to ask of the media, particularly as
patients' lives and health are at stake.
Pittenger: I think the
first misconception is that it is a
long way off; it's not, at least not in
every field. The second misconception is that success in applying stem cells to
health issues will be "all-
curing"—it will not. Rather, it will be another powerful
tool for treating a variety of health problems.
ALSO FROM OUR
AUGUST ISSUE SPECIAL REPORT: Root to stem
In new survey, we try to get to the bottom of perceptions on stem cells and other R&D efforts By Jeffrey Bouley, ddn Managing Editor Editorial: Embryonic stem cell research: A Dickey-Wicker of a situation Isn't it about time Congress revisited what is essentially an afterthought on a 15-year-old appropriations bill, clearly articulated the facts and concerns about hESC research and put forth a specific policy on the matter? By Amy Swinderman, ddn Chief Editor Code: E081131 Back |
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