Stem Cells in the Treatment of Diabetes: Therapeutic Potential and Ethical Considerations

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 permissible?

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 level, however,
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 developmental potential;
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 improve diabetic
symptoms (4).

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 undifferentiated state.
Because of their uncontrolled growth, embryonic stem cells may have tumor-forming potential
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 differentiated to
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 lethally irradiated
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 differentiation
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 manner (8).

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 of embryonic
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.

References:

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 Progress and
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 for the
elusive pancreatic stem cell? Journal of Clinical Investment. 111:799-801.

4. Hori, Y. et al. 2002. Growth inhibitors promote differentiation of insulin-producing
tissue from embryonic stem cells. Proceedings of the National Academy of Sciences.
USA. 99:16105- 16110.

5. Ianus, A. et al. 2003. In vivo derivation of glucose-competent pancreatic endocrine
cells from bone marrow without evidence of cell fusion. Journal of Clinical Investment.
111:843-850.

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. Journal
of Medical Ethics. 26: 166-170

8. Congregation for the Doctrine of the Faith. Donum Vitae. I:1-5. Boston: St.
Paul Editions, 1987.