Text 11943, 217 rader
Skriven 2005-04-20 21:14:32 av Alan Hess
     Kommentar till en text av Vern Humphrey
Ärende: why embryonic cells?
============================
Vern,

I asked Dr. Wise Young, a top spinal cord injury researcher and owner of the
CareCure website, why there's so much interest in embryonic stem cells, as
adult stem cells don't invoke controversy and have already been used in some
treatments.  Here's his reply (posted with permission, and including the site
url sciwire.com.  The thread discussing this is in the Cure forum of that
site.)

******

WHY ARE EMBRYONIC STEM CELLS IMPORTANT?

Wise Young, Ph.D., M.D.
W. M. Keck Center for Collaborative Neuroscience
http://sciwire.com

Opponents of embryonic stem cell research often argue that embryonic stem cell
research is not necessary because adult stem cells from bone marrow or
umbilical cord blood cells are already curing diseases, are more likely to cure
diseases, and that adult stem cells would not be rejected by the immune system
when transplanted. They are troubled by the cloning because they oppose
creating an embryo in order to harvest its stem cells. Finally, they point out
that current methods of collecting embryonic stem cells are inefficient and
cloning embryonic stem cells may not be a practical method of producing cells
for transplantation purposes. These arguments are partly true but are
misleading and do not justify the current restrictions of human embryonic stem
cell research. Let us consider some of the most frequently cited arguments for
or against adult and embryonic stem cells.

1. Are adult stem cells already curing diseases? Some opponents of embryonic
stem cell research say that embryonic stem cells have never cured any condition
while adult stem cells are already curing many diseases. Bone marrow and
umbilical cord blood stem cells have been used for over two decades to treat
blood-making (hematopoietic cells) disorders, such as sickle cell anemia,
thalassemia, radiation or chemotherapy induced bone marrow damage, and
autoimmune diseases. Bone marrow stem cell transplants may accelerate and
improve healing from heart attacks (myocardial infarcts) or failing hearts
(congestive heart failure). However, there is no credible evidence yet that
bone marrow stem cells are replacing heart cells. Bone marrow cells may be
releasing factors that help hearts heal faster. Neither bone marrow nor
umbilical cord blood stem cells, or other types of adult stem cells, have cured
neurological conditions, such as brain or spinal cord injury, amyotrophic
lateral sclerosis, multiple sclerosis, Alzheimer's disease, Parkinson's
disease, or non-neurological diseases such as diabetes, liver damage from
hepatitis, and other currently incurable conditions. We do not know enough now
to predict whether adult or embryonic stem cells would be better or which would
be more effective.. Many animal studies have shown beneficial effects of
embryonic stem cell treatments of animal models of diseases. Human embryonic
stem cells have not yet been transplanted into humans. There are no
restrictions on adult bone marrow or umbilical cord blood research at all while
U.S. federal government signficantly restricts funding of human embryonic stem
cell research.

2. Do adult stem cells circumvent the problem of immune rejection? It is true
that autologous grafts, i.e. adult stem cells taken from a person and
transplanted into the same person, would not be rejected by the immune system.
However, autologous grafts cannot be used for many conditions. First,
autologous grafts are not useful for most genetic diseases. For example, there
is no point in taking bone marrow from a person with a genetic disease such as
sickle cell anemia or thalassemia and then transplanting these cells back into
the same person. Heterologous grafts, i.e. transplant from one person to
another, are necessary. Second, autologous bone marrow grafts cannot be used to
treat many autoimmune diseases, such as multiple sclerosis, diabetes, lupus
erythematosus, scleroderma, etc. The transplanted bone marrow will produce
cells with the same autoimmune tendencies. Third, bone marrow transplants often
cause graft-versus-host disease where the transplanted cells regard the host
body as "foreign" and attack it. As much as 50% of heterologous bone marrow
transplants cause graft-versus-host disease with a high mortality rate. Fourth,
even closely matched heterologous bone marrow transplants require
immunosuppression. Destroying the bone marrow usually does this. Finally,
umbilical cord blood does not produce as much immune response or as severe
graft-versus-host disease. Human embryonic stem cells, because they are
immature, are even less immunogenic and do not produce graft-versus-host
disease.

3. Are adult stem cells safer than embryonic stem cells for treatment of
neurological disorders? Autologous transplants are very attractive for treating
non-genetic diseases. For example, they would be an ideal treatment for
traumatic brain and spinal cord injury, Parkinson's disease, stroke, and
non-genetic conditions. However, heterologous transplants may be required for
genetic conditions such Alzheimer's disease or amyotrophic lateral sclerosis.
Even when bone marrow cells are carefully matched for histocompatibility,
prolonged immune suppression may be required for engraftment. If selected stem
cells are transplanted, particularly into brain or spinal cord, graft-vs. host
disease would be unlikely. On the other hand, bone marrow transplants have a
high complication rate, with a 20-50% incidence of graft-versus-host disease
and 20-30% mortality rates. For these reasons, heterologous bone marrow
transplants are seldom carried out except for life-threatening conditions. In
contrast, embryonic stem cell transplants may not require as much or as
prolonged immunosuppression because they do not express as many immunogenic
proteins. Cloned embryonic stem cells that are genetically matched for the
person should pose even less immunogenic risk.

4. Do embryonic stem cells cause tumors? There are some claims that embryonic
stem cells are more likely to cause tumors. All cells have the potential to
cause tumors, particularly if they are grown for long periods in culture.
Prolonged culturing increases the risk of malignant transformation of the
cells. Immaturity of cells also may increase the likelihood of tumor formation.
Some stem cells will not respond to all tissue factors and may produce the
wrong type of cells, too many cells, or cells that transgress tissue
boundaries. Cells with any of these three behaviors would be called a tumor.
Because embryonic stem cells are often grown for long periods of time in
culture, they have more of an opportunity to undergo malignant transformation.
Because embryonic stem cells are immature compared to adult stem cells, they
may not possess receptors to all tissue factors. However, much evidence now
suggests that embryonic stem cells can be matured and pre-differentiated in
culture before transplantation and that such cells are unlikely to produce
tumors. This is a risk but not an insurmountable risk.

5. Are adult stem cells more likely to result in cures for diseases than
embryonic stem cells? Adult bone marrow or umbilical cord blood stem cells have
been used to treat hematopoietic disorders for over 20 years. As pointed out
above, heterologous bone marrow grafts may cause serious complications and are
currently only used under the most dire circumstances. Umbilical cord blood
transfusions show promise and presents less risk but appear to be less
effective. Although some scientists have claimed that bone marrow mesenchymal
stem cells can be induced to produce neurons and other cells under certain
circumstances, their ability to do so is limited and substantial manipulation
of the cells is required. In contrast, embryonic stem cells readily produce all
types of cells, including neurons, insulin-producing cells, muscle, skin, and
heart cells, both in culture and after transplantation. Embryonic stem cells
also grow faster in culture and can be easily modified to produce specific
cells with specific functions. We are perhaps expecting too much from adult
stem cells when we transplant them into different tissues and expect them to
fix disparate problems such as replacing insulin-producing cells, promote
regeneration, remyelinate axons, repair heart tissues, and restore function to
diverse organs. From this perspective, embryonic stem cells possess a
significant advantage over adult stem cells. Because they grow indefinitely in
culture, they can be produced in large numbers and be optimized to have more
predictable and beneficial behavior after transplantation. At the present, we
don't know which is more likely to result in cures for diseases.

6. Is cloning necessary for embryonic stem cells to be used for
transplantation? In biology, cloning means simply to produce cells with the
same genes. Cellular cloning unfortunately has been associated with
"reproductive cloning" or production of an individual with the same genes. One
method of cloning embryonic stem cells is to transfer a nucleus into an egg and
then trick the egg into producing stem cells. Called somatic cell nuclear
transfer (SCNT), this method produces stem cells that have the same genes as
the transferred nucleus. This method of cloning stem cells is currently
inefficient, requiring dozens of eggs. In my opinion, cloning is not necessary
for embryonic stem cells to be used for therapy. Doctors have successfully
transplanted cells (blood) and organs (kidney, heart, liver, pancreas) for many
decades without cloning. If the stem cells are carefully matched for
histocompatibility genes (HLA) and immunosuppressive therapies are used, the
cells will engraft. It is also possible to develop embryonic stem cell lines
that express a limited set of histocompatibility antigens that would match 90%
of people. Finally, immune rejection is not necessarily bad. The immune system
eliminates cancer or excess cells. We may want the immune system to eliminate
the cells after they have finished their work. In any case, much work needs to
be done on cloning before it can be used clinically. For example, I don't think
that it would be harmful to have 3-year moratorium on cloning of human
embryonic stem cells but allow animal and human embryonic stem cell research to
go forward. On the other hand, a ban of SCNT would be a serious mistake because
it is a general technique that is important for many other clinical
applications.

7. Are embryonic stem cells practical? At the present, we do not have enough
cells from any source that can be used to treat millions of people. For
example, the world supply of umbilical cord blood is about 200,000 units. This
is barely sufficient to satisfy the needs of 12,000 pediatric patients who need
umbilical cord stem cells every year to treat their hematopoietic disorders.
Although many laboratories have been trying for decades to grow stem cells from
bone marrow, umbilical cord, placental, and other postnatal sources of stem
cells, no reliable method is available to produce sufficient diversity and
amounts of bone marrow or umbilical cord stem cells to treat millions of
people. If any stem cell turned out to be useful for any of the major diseases,
we do not have enough cells to treat even a tiny fraction of the people.
Because they grow indefinitely in culture, embryonic stem cells provide a
possible inexhaustible supply of stem cells that can treat millions of people.
A cell bank with several thousand lines of human embryonic stem cells, for
example, would be very helpful to satisfy current therapeutic and research
needs.

8. What other ways can human embryonic stem cells help cure diseases? Opponents
of embryonic stem cell research seldom mention one important use of human
embryonic stem cells. An embryonic stem cell line derived from a person with a
genetic disease would be a very powerful tool to study that genetic disease.
For example, if we had an embryonic stem cell lines from somebody with
Alzheimer's, amyotrophic lateral sclerosis, Huntington's disease, diabetes,
rheumatic arthritis, lupus erythematosus, etc. the cells can be used to assess
mechanisms and treatments. At the present, we have to use animal models or
human cadaver materials. Availability of human embryonic stem cell lines will
allow large-scale screening of drugs and other treatments. Finally, many
parents who use in vitro fertilization methods may have specific genetic
conditions causing infertility. Eggs from infertility clinics may provide
insight into genetic causes of infertility. Last but not least, the
availability of such human disease-specific stem cell lines should reduce use
of animals for studying human disease.

In summary, adult bone marrow and umbilical cord blood stem cells have long
been used to treat hematopoietic disorders. Obtaining stem cells from one part
of the body and transplanting to another would circumvent immune rejection but
most genetic diseases cannot be treated with such transplants. Bone marrow
grafts tend to be immunogenic and cause graft-versus-host disease where
transplanted immune cells attack the host. Human umbilical cord blood
transplants are less immunogenic and cause less serious graft-versus-host
disease. Human embryonic stem cells are even less immunogenic and do not cause
graft-versus host disease. Stem cells may produce tumors after transplantation
if they do not respond to all tissue factors, produce the wrong type or numbers
of cells that do not respect tissue boundaries. All cells have some potential
for malignant transformation. Differentiating stem cells in culture before
transplantation reduces the risk of tumors. Cloning should produce genetically
matched stem cells but we have much work to do before cloning can be applied
clinically. Doctors have been transplanting cells and organs for many years
without cloning. Embryonic stem cell research should go forward, even without
cloning. We do not now have an adequate stem cell supply to treat even a small
fraction of people who may benefit from stem cell therapies. Embryonic stem
cells can be grown indefinitely to treat millions of people. Human embryonic
stem cell lines obtained from people with specific genetic diseases will
greatly accelerate research on many genetic diseases, including infertility,
and will reduce the use of animals. Thus, it is important not to close the door
on human embryonic stem cell research.

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