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echo: abled
to: Alan Hess
from: Janis Kracht
date: 2005-04-21 11:56:20
subject: why embryonic cells?

Hi Alan,

Great post.  Thanks for posting that and thanks to Dr. Young :)

Take care,
Janis

> 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 cur
>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 conditio
> 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 cure
> 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 woul
> 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 whil
>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 t
> 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 ofte
> 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 treatin
> 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 hav
> 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 al
> 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 an
> 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 man
> 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 thin
> 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 t
>go forward. On the other hand, a ban of SCNT would be a serious mistake becaus
> 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 nee
> umbilical cord stem cells every year to treat their hematopoietic disorders.
>Although many laboratories have been trying for decades to grow stem cells fro
> 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? Opponent
> 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 number
> 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 doo
> on human embryonic stem cell research.

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