Stem Cells: A Primer, National Institutes of Health, May 2000
Fuente: http://www.nih.gov/news/stemcell/primer.htm
NATIONAL INSTITUTES OF HEALTH May 2000 |
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Stem Cells: A Primer
- Transplant of healthy heart muscle cells could provide new hope for patients with chronic heart disease whose hearts can no
longer pump adequately. The hope is to develop heart muscle cells from human pluripotent stem cells and transplant them into
the failing heart muscle in order to augment the function of the failing heart. Preliminary work in mice and other animals has
demonstrated that healthy heart muscle cells transplanted into the heart successfully repopulate the heart tissue and work
together with the host cells. These experiments show that this type of transplantation is feasible.
- In the many individuals who suffer from Type I diabetes, the production of insulin by specialized pancreatic cells, called islet
cells, is disrupted. There is evidence that transplantation of either the entire pancreas or isolated islet cells could mitigate the
need for insulin injections. Islet cell lines derived from human pluripotent stem cells could be used for diabetes research and,
ultimately, for transplantation.
While this research shows extraordinary promise, there is much to be done before we can realize these innovations.
Technological challenges remain before these discoveries can be incorporated into clinical practice. These challenges, though
significant, are not insurmountable.
First, we must do the basic research to understand the cellular events that lead to cell specialization in the human, so that we
can direct these pluripotent stem cells to become the type(s) of tissue needed for transplantation.
Second, before we can use these cells for transplantation, we must overcome the well-known problem of immune rejection.
Because human pluripotent stem cells derived from embryos or fetal tissue would be genetically different from the recipient,
future research would need to focus on modifying human pluripotent stem cells to minimize tissue incompatibility or to create
tissue banks with the most common tissue-type profiles.
The use of somatic cell nuclear transfer (SCNT) would be another way to overcome the problem of tissue incompatibility for
some patients. For example, consider a person with progressive heart failure. Using SCNT, the nucleus of virtually any somatic
cell from that patient could be fused with a donor egg cell from which the nucleus had been removed. With proper stimulation
the cell would develop into a blastocyst: cells from the inner cell mass could be taken to create a culture of pluripotent cells.
These cells could then be stimulated to develop into heart muscle cells. Because the vast majority of genetic information is
contained in the nucleus, these cells would be essentially identical genetically to the person with the failing heart. When these
heart muscle cells were transplanted back into the patient, there would likely be no rejection and no need to expose the patient
to immune-suppressing drugs, which can have toxic effects.
Adult Stem Cells
As noted earlier, multipotent stem cells can be found in some types of adult tissue. In fact, stem cells are needed to replenish the
supply cells in our body that normally wear out. An example, which was mentioned previously, is the blood stem cell.
Multipotent stem cells have not been found for all types of adult tissue, but discoveries in this area of research are increasing.
For example, until recently, it was thought that stem cells were not present in the adult nervous system, but, in recent years,
neuronal stem cells have been isolated from the rat and mouse nervous systems. The experience in humans is more limited. In
humans, neuronal stem cells have been isolated from fetal tissue and a kind of cell that may be a neuronal stem cell has been
isolated from adult brain tissue that was surgically removed for the treatment of epilepsy.
Do adult stem cells have the same potential as pluripotent stem cells?
Until recently, there was little evidence in mammals that multipotent cells such as blood stem cells could change course and
produce skin cells, liver cells or any cell other than a blood stem cell or a specific type of blood cell; however, research in
animals is leading scientists to question this view.
In animals, it has been shown that some adult stem cells previously thought to be committed to the development of one line of
specialized cells are able to develop into other types of specialized cells. For example, recent experiments in mice suggest that
when neural stem cells were placed into the bone marrow, they appeared to produce a variety of blood cell types. In addition,
studies with rats have indicated that stem cells found in the bone marrow were able to produce liver cells. These exciting
findings suggest that even after a stem cell has begun to specialize, the stem cell may, under certain conditions, be more flexible
than first thought. At this time, demonstration of the flexibility of adult stem cells has been only observed in animals and limited
to a few tissue types.
Why not just pursue research with adult stem cells?
Research on human adult stem cells suggests that these multipotent cells have great potential for use in both research and in the
development of cell therapies. For example, there would be many advantages to using adult stem cells for transplantation. If we
could isolate the adult stem cells from a patient, coax them to divide and direct their specialization and then transplant them
back into the patient, it is unlikely that such cells would be rejected. The use of adult stem cells for such cell therapies would
certainly reduce or even avoid the practice of using stem cells that were derived from human embryos or human fetal tissue,
sources that trouble many people on ethical grounds.
While adult stem cells hold real promise, there are some significant limitations to what we may or may not be able to accomplish
with them. First of all, stem cells from adults have not been isolated for all tissues of the body. Although many different kinds of
multipotent stem cells have been identified, adult stem cells for all cell and tissue types have not yet been found in the adult
human. For example, we have not located adult cardiac stem cells or adult pancreatic islet stem cells in humans.
Secondly, adult stem cells are often present in only minute quantities, are difficult to isolate and purify, and their numbers may
decrease with age. For example, brain cells from adults that may be neuronal stem cells have only been obtained by removing a
portion of the brain of epileptics, not a trivial procedure.
Any attempt to use stem cells from a patient's own body for treatment would require that stem cells would first have to be
isolated from the patient and then grown in culture in sufficient numbers to obtain adequate quantities for treatment. For some
acute disorders, there may not be enough time to grow enough cells to use for treatment. In other disorders, caused by a
genetic defect, the genetic error would likely be present in the patient's stem cells. Cells from such a patient may not be
appropriate for transplantation. There is evidence that stem cells from adults may have not have the same capacity to proliferate as younger cells do. In addition, adult stem cells may contain more DNA abnormalities, caused by exposure to daily living, including sunlight, toxins, and by expected errors made in DNA replication during the course of a lifetime. These potential weaknesses could limit the usefulness of adult stem cells.
Research on the early stages of cell specialization may not be possible with adult stem cells since they appear to be farther
along the specialization pathway than pluripotent stem cells. In addition, one adult stem cell line may be able to form several,
perhaps 3 or 4, tissue types, but there is no clear evidence that stem cells from adults, human or animal, are pluripotent. In fact,
there is no evidence that adult stem cells have the broad potential characteristic of pluripotent stem cells. In order to determine
the very best source of many of the specialized cells and tissues of the body for new treatments and even cures, it will be vitally
important to study the developmental potential of adult stem cells and compare it to that of pluripotent stem cells.
Summary
Given the enormous promise of stem cells to the development of new therapies for the most devastating diseases, it is important
to simultaneously pursue all lines of research. Science and scientists need to search for the very best sources of these cells.
When they are identified, regardless of their sources, researchers will use them to pursue the development of new cell therapies.
The development of stem cell lines, both pluripotent and multipotent, that may produce many tissues of the human body is an
important scientific breakthrough. It is not too unrealistic to say that this research has the potential to revolutionize the practice
of medicine and improve the quality and length of life.
1 Michael Shamblott, et al, Derivation of pluripotent stem cells from cultured human primordial germ cells. PNAS, 95:
13726-13731, Nov. 1998.
James Thomson, et al, Embryonic stem cell lines derived from human blastocysts. Science, 282: 1145-1147, Nov. 6, 1998.