Stem Cells in the Treatment of Diabetes: Therapeutic Potential and Ethical
by Catherine Mastroieni
a paper prepared for "Ethical Issues in Biotechnology and Genetics,"
an undergraduate class in the Biology Department of Santa Clara University
Diabetes mellitus affects 18 million people in the U.S. alone (8.7% of
the population) and more than 190 million worldwide. The prevalence of
diabetes has increased alarmingly in the past three decades and, corresponding
to global dietary and lifestyle trends, is projected to nearly double
in the next ten years (1). Although diabetes can be treated, serious complications
from improperly managed diabetes are common and can lead to death. Recent
reports suggest that one of the most promising potential treatments may
come from the use of stem cells, undifferentiated cells that can be coaxed
into becoming insulin-producing islet-like cells that reduce diabetes
symptoms in mice (2).
There is one ethical catch, however: stem cells can be derived from a
number of sources, including adult tissues, but the purest source of stem
cells with the greatest therapeutic potential is early-stage embryos.
The process of deriving stem cells destroys the embryo. Does the human
embryo have moral status that would proscribe its destruction, regardless
of the potential good that might be achieved? If so, are there still avenues
of stem cell research that are both scientifically viable as well as morally
Diabetes is a disease that results from the body's inability to maintain
consistent levels of glucose (the main energy source for cells) in the
blood. In a healthy individual, blood glucose levels are kept within a
certain range by insulin, a hormone that aids the uptake of glucose by
cells. The release of insulin in response to blood glucose levels is coordinated
by clusters of cells in the pancreas called islets; residing in these
islets are the beta cells, the cells that actually produce (and release)
insulin. Diabetes develops when there too few functioning beta cells (2).
Diabetes can be controlled by frequent monitoring of blood glucose levels
and either medication
(type II diabetes) or insulin injections (type I diabetes), but improper
management of the disease results in serious complications, including
heart and kidney damage, blindness and loss of extremities. One promising
novel treatment for type I diabetes is pancreatic islet cell transplantation,
but this therapy is limited by the number and availability of donated
organs for transplant. If stem cells can be induced to differentiate into
functional islet cells in the lab, they may form a renewable source for
transplantation, allowing this cell-based treatment to become available
on a practical scale (3, 4).
Stem cells are self-renewing, unspecialized cells that give rise to multiple
specialized cell types
through a process of differentiation. Theoretically, stem cells could
be induced in the laboratory
to become any specialized body cell type, including pancreatic islet cells,
and then transplanted
back into a patient to replace diseased or damaged tissue (2). Transplantation
of stem cells or
stem-cell derived tissue into human patients has not yet reached the clinical
and many questions remain regarding the safety and efficacy of such therapies.
In order to better gauge the therapeutic potential of stem cells, much
basic research and
animal model testing is currently being conducted. Scientists have focused
on stem cells from
two sources: early-stage embryos and stem cells from adult tissue. Embryonic
and adult stem
cells have different characteristics and are thought to have different
as such, each type of stem cell presents distinct challenges as well as
promise for forming the
basis of an eventual treatment for diabetes.
Embryonic stem cells are derived from the inner cell mass of blastocysts
approximately five days
after fertilization in vitro, and appear to have the greatest therapeutic
potential. These cells
grow indefinitely in the lab and are termed pluripotent, as they can develop
into any of the
cell types of the body (2). Scientists have identified specific growth
inhibitors that induce mouse
embryonic stem cells to adopt, in vitro, various characteristics of pancreatic
islet cells, including
insulin production, glucose-dependent insulin release and formation of
islet-like aggregates. Also,
when transplanted into diabetic mice, these islet-like clusters significantly
The exact pathways that embryonic stem cells take to become pancreatic
cells are yet to be
identified, however, and embryonic stem cells themselves present a number
of scientific challenges.
In general, embryonic stem cells are hard to maintain in culture in their
Because of their uncontrolled growth, embryonic stem cells may have tumor-forming
if not fully differentiated before transplantation into patients. There
is also the risk of immune
rejection following transplantation, so patients receiving the transplants
would likely have to
be maintained on immune-suppressant medication.
Adult stem cells, which are derived from mature somatic tissues, may
avoid the issue of
immune rejection (if the stem cells are taken from the patient who later
receives the transplant)
but present distinct challenges of their own. Adult stem cells do not
grow indefinitely in the
lab and, although they can be found in a great number of tissues, these
special cells are
generally rare and hard to identify. In addition, adult stem cells are
thought to have a more
limited differentiation profile than embryonic cells, with only the capacity
to differentiate into
the specialized cells of the tissue from which they were derived (e.g.
a brain stem cell could
become a neuron but not a blood cell).
Preliminary studies in which adult stem cells of non-pancreatic origin
become islet-like cells suggest that adult stem cells may have greater
plasticity, or ability
to develop into a greater number of cell types than previously believed.
In one case,
scientists demonstrated that bone marrow-derived cells transplanted into
mice are able to differentiate into functional, insulin-producing islet
cells in the pancreases
of the recipients (5). It is not known, however, whether these differentiated
cells were the
progeny of hematopoitic stem cells (which normally do not give rise to
pancreatic cells) or
pancreatic stem cells that happen to reside in the bone marrow (3, 5).
In another study
adult hepatic oval cells, stem cells of the liver that do not normally
give rise to pancreatic
tissue, were shown to differentiate into pancreatic islet-like clusters
in vitro that are able
to reverse diabetic symptoms in mice upon transplantation (6).
The main ethical concern with stem cell research is balancing the pursuit
of a potential therapy
for diabetics with the proper respect for and protection of human life,
an immediate issue when
considering the destruction of living human embryos that is involved in
the derivation of embryonic
stem cells. An embryo is a unique human entity whose biological identity
is determined from the
moment of fertilization; this identity is unchanging through any subsequent
and growth. The post-fertilization splitting of some zygotes into twins
does not change the fact
that the identity of human being has its beginning at one single point
in time, and from that point
on is the identity of a unique human individual. The development of a
human being is a
continuum through life and, while it affects the physical aspect of a
human being (and that
dramatically in the first years of life) it does not determine personhood,
which exists from
the moment a human life is present (7, 8).
Natural law, or those rules for action that all can know through reason
and observation of
the world, states that all human persons possess certain basic rights
including the right to
life and physical integrity. Because these rights, or justifiable claims
on others, flow from
each human person's intrinsic dignity as sharers in a common human nature,
all living human
beings must be regarded as persons and treated in a morally equivalent
If the human embryo is a person, then he or she cannot be used as a means
toward any end,
however good. No projected therapeutic good that may come from the use
stem cells can outweigh the immediate harm (death) to the human embryo
when its stem
cells are extracted. Therefore, research that involves the derivation
of stem cells from living
human embryos is morally unacceptable, even if the projected benefits
can be gotten in no
other way. The creation of "surplus" embryos that one is not
planning to implant, a routine
part of in vitro fertilization procedures, must also be rejected (8).
Other scientifically and ethically viable avenues of stem cell research
do exist that appear
to hold great promise for the eventual treatment of diabetes, including
the use of adult
stem cells, and these should be pursued. Although much basic research
remains to be done,
adult stem cells appear to have great therapeutic potential and may even
have an edge
over embryonic cells, in that they avoid issues of immune rejection.
1. U.N. Foundation. National Journal. 14 Nov. 2003. "World Diabetes
Day Reveals Scope
of Problem, Breakthrough." Accessed 11 Dec. 2003.
2. U.S. Department of Health and Human Services. Stem Cells: Scientific
Future Research Directions. June 2001. <http://www.nih.gov/news/stemcell/scireport.htm>
3. Lee, V. and M. Stoffel. 2003. Bone Marrow: an extra-pancreatic hideout
elusive pancreatic stem cell? Journal of Clinical Investment. 111:799-801.
4. Hori, Y. et al. 2002. Growth inhibitors promote differentiation of
tissue from embryonic stem cells. Proceedings of the National Academy
USA. 99:16105- 16110.
5. Ianus, A. et al. 2003. In vivo derivation of glucose-competent pancreatic
cells from bone marrow without evidence of cell fusion. Journal of Clinical
6. Yang, L. et al. 2002. In vitro trans-differentiation of adult hepatic
stem cells into
pancreatic endocrine hormone-producing cells. Proceedings of the National
Academy of Sciences. USA. 99:8078-8083.
7. Meyer, J. June 2000. Human embryonic stem cells and respect for life.
of Medical Ethics. 26: 166-170
8. Congregation for the Doctrine of the Faith. Donum Vitae. I:1-5. Boston:
Paul Editions, 1987.