Back to Focus on Stem Cells articles Sorting Out the Confusion - An Update on Stem CellsPrepared by Ida Chow (SDB Executive Officer, [email protected]) and Gary Radice (SDB Education Committee Member, [email protected]). September 2001 The Dog Days of August have been indeed crazy, especially for the folks at the National Institutes of Health and the U.S. Department of Health and Human Services, trying to answer all the questions from the White House and the Congress about human embryonic stem cells. The hype mainly (but not solely) in the popular media has also given a sense of urgency to the issue that cannot be solved overnight. We hope this piece will help those not directly involved with the subject (including many of us, developmental biologists) to put things in perspective and decide on their own the merits on the use of human embryonic stem cells for research and therapy purposes. We will refer to, and include links to sound documents and articles that we feel are relevant to this discussion, which by no means constitute a complete survey of the literature. Firstly, the Society for Developmental Biology's positions on:
Just Released News! 1. Stem cell research and cloning: the
science behind the headlines
This fundamental question about cell differentiation during embryonic
development has puzzled and challenged developmental biologists for
many years. Learning the answers has been difficult, because
typically these decisions are made only once or a few times in a
small number of cells inside each embryo at early stages of
development. The excitement surrounding stem cell research comes from
the opportunity to study these genetic decisions as they occur in
large numbers of cells outside the embryo, growing in culture where
they can be controlled and studied more easily. The hope is that
studying isolated stem cells will finally allow us to learn the exact
steps needed to convert an undifferentiated cell into any specific
cell type. This knowledge would have extensive therapeutic
implications since it could make it possible to grow replacement
cells for those damaged by disease.
"Cloning" is not the same
as stem cell research, but can encompass many different technologies,
including the use of stem cells. In this context, cloning means
creating a new individual by replacing an egg cell nucleus (with only
one-half of the genetic complement) with a nucleus from the body cell
of a different individual (containing the full genetic complement).
This donated nucleus then directs the development of a new embryo,
with the same genes as the donor. The donor nucleus potentially could
come from another embryo, an adult, or a stem cell growing in
culture. 2. Feasibility and limitations in the use of
embryonic (ES), fetal (FS) and adult (AS) stem cells. ES cells: Embryonic stem cells are derived from the inner cell mass of a human blastocyst, a stage of very early development, when the embryo is still a microscopic ball of about 100 dividing cells. When cultured in plastic dishes under appropriate conditions they are capable of dividing indefinitely and differentiating into almost all the more than 200 cell types of the body. The pluripotency of these ES cells has been repeatedly demonstrated in mouse and other laboratory mammals in the past twenty years. However, these cells from the inner cell mass will not normally form the placenta, which is formed by cells coming from the outer cell (trophoblastic) layers of the blastocyst. Thus, ES cells will not give rise to a fetus even if implanted into a woman's womb. FS cells: The fetal stem cells may be isolated from germ cells or other developing organs of fetuses. When cultured in dishes they behave similarly to the ES cells. FS cells derived from germ cells have also been shown to be pluripotent, while less is known about the cells derived from other fetal tissues. AS cells: In an adult, the tissues that normally turn over and replace themselves, such as the skin, the lining of the stomach and intestines and the blood cells, contain undifferentiated cells called stem cells. These adult stem cells undergo cell division, thus preserving the undifferentiated cell population, and some differentiate into the appropriate cell types to replace those that died in their natural life span. For a long time it was believed that these stem cells would only differentiate into cells of the same tissue, that is, skin stem cells into skin and blood stem cells into blood. It was also believed that some cell types, such as the neurons and the heart muscle cells do not have these precursor cells, and that once the neurons and the heart cells died they could not be replaced. These concepts are now being reevaluated. In the last two years, several reports have revealed the ability of cells obtained from adult tissues in mouse and human to differentiate into cell types that belong to other tissue types. For example, cells from the bone marrow have been shown to be capable of transforming into muscle and other cell types. In addition, precursor cells obtained from adult mouse central nervous system have been reported to transform into neurons and other support cells when cultured under specific conditions. These unexpected findings have opened new hopes for AS cells. Since these reports are very recent and still largely unconfirmed by different research groups, the pluripotency of the AS cells remains to be explored by more studies. In addition, little is known about the properties of these AS cells, including their life span, genetic diversity and stability of the derived cell lines. The number of divisions these AS cells can undergo remains undetermined. Whether these undifferentiated, precursor cells derived from adult mammals (including humans) are truly stem cells with indefinite cell division capability and pluripotency remains to be elucidated. 3. Minimum number of cell lines necessary
for therapeutic use One possible way to overcome this mismatch is to extract adult stem cells from the patient, and then to coax them to multiply in large numbers and to differentiate into the cell type of interest. Another means is to use the technique of somatic cell nuclear transfer to produce a blastocyst, by injecting the nucleus from a body cell of the patient into an egg whose own nucleus has been removed, and then triggering the egg to divide by applying an electrical current. Embryonic stem cells derived from the inner cell mass can then provide cells of the patient's exact match for therapeutic use. Both these approaches depend on further understanding of the cellular and molecular mechanisms regulating the cell differentiation processes, and on technologies to produce large numbers of desired cells. In addition, the success of adult stem cells can only be realized if identification and extraction from the person can be done effectively. We don't yet know what the effective and minimum number of stem cell lines is, to order to cover all the human genetic variations. We are, however, optimistic that answers will be available when more studies are carried out with current cell lines.
5. Legislative
considerations One characteristic of the American legislation is that some restrictions are applied to federally funded activities, whereas the same activities may not have any limitation if carried out with private funds. This is especially significant in the areas of medical practice, in regards to the assisted reproductive technologies (in vitro fertilization, for example) and biomedical research, as we see now with the human embryonic stem cells. Currently, investigators funded by private organizations may derive cells from, and conduct experiments with human embryos; whereas those receiving federal monies such as from the NIH cannot. This disparity, added to the inherent "proprietary" rights of private companies and extensive public expression of their opinions by activist groups, complicates the matter even more in this country. Bills on stem cells (and other issues) introduced in the US Congress can be found at: http://thomas.loc.gov
6. Ethical considerations Due to the fact that these issues touch upon many sensitive areas; including political, traditional, cultural and religious concerns, there will likely never be complete agreement in all areas. Perhaps, the best that can be hoped for, is a general consensus to work toward the greater good, that being the most beneficial results for the greatest number of people. References and linksOn SDB Website
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