Bone Marrow May Restore Cells Lost in Vision Diseases

GAINESVILLE, Fla. — University of Florida scientists
conducting experiments with mice have found evidence that
the body naturally replenishes small amounts of cells in
the eye essential for healthy vision.

The finding may shatter the belief that a cell layer vital
for eyesight called the retinal pigment epithelium, or RPE,
is a nonrenewable resource, say researchers writing in a
recent issue of Investigative Ophthalmology & Visual
Science.

RPE plays a vital role in our visual health by forming the
outer barrier of the retina and supporting the function of
cells that receive light. Damage to RPE is present in many
diseases of the retina, including age-related macular
degeneration, which affects more than 1.75 million people
in the United States.

With evidence that the body does indeed regenerate these
cells in small amounts, scientists can focus on ways to
accelerate natural healing processes to treat sight-robbing
injuries or diseases.

“What this tells us is for problems such as age-related
macular degeneration, we should be able to harvest stem
cells to help repair the damage,” said senior author Edward
Scott, a professor of molecular genetics at the UF Shands
Cancer Center and director of the Program in Stem Cell
Biology and Regenerative Medicine at UF’s College of
Medicine. “The question is whether we can do it in a
patient.”

Scientists widely believe that RPE is a finite resource.
The same belief used to be held about brain cells — people
who suffered from trauma, stroke or disease formerly faced
no hope of growing new cells to replace dead ones.

Then, in the late 1990s, when scientists began to report
findings of brain cell growth in humans and monkeys later
in life, focus turned toward understanding the mechanisms
to regenerate cells in the brain.

Now, UF researchers believe it may be possible to also grow
new cells in the retina to replace cells lost to injury or
disease.

“In people, retinal pigment epithelium can become damaged
with age,” said Jeffrey Harris, a graduate student in the
molecular cell biology program in UF’s College of Medicine
and first author of the paper. “Factors like smoking and
diet also come into play. The problem is without these
cells, the rods and cones — our primary cells for vision —
die. If we can regenerate the retinal pigment epithelium,
it could make a big difference in our visual health.”

Scientists were able to detect that RPE cells indeed appear
to be naturally replenished in the test animals by
transplanting bone marrow cells from normal male mice into
albino females with two different types of acute RPE
injury.

Bone marrow contains stem cells, which have the
extraordinary abilities to home in on injuries and possibly
regenerate other cell types in the body. In this case, the
cells were transplanted to confirm that bone marrow does
regenerate the injured RPE. It was easier to track male,
pigment-producing cells in female, albino recipients,
Harris said.

Chemical and microscopic analysis showed the cells that
traveled to the injury site and transformed into RPE indeed
had male genetic characteristics. Furthermore, these cells
were capable of producing pigment — a colorful indication
that the RPE could only have arisen from the donor bone
marrow stem cells.

“We did not use a direct model of age-related macular
degeneration,” Scott said. “But we now know that when RPE
is injured, it can be replaced in certain situations. It
gives us growth factors, cell pathways and other different
places to look at to find reasons why the disease is
occurring.”

Researchers want to discover ways to mobilize an elderly
patient’s own cells to travel to the injury site to make
repairs.

“The dogma has been that we’re born with a fixed amount of
RPE, but there is growing evidence retinal progenitor cells
exist in the adult,” said Lawrence Rizzolo, a Yale
University associate professor of anatomy and experimental
surgery and of ophthalmology and visual science who was not
involved in the research. “To derive cells of neuronal
lineage from cells of bone-marrow lineage is significant,
if the finding stands up to the test of time. Compared to
RPE transplantation, there are a lot of advantages if
someone’s own bone marrow could supply the cells, because
it’s a ready source and the cells would not be rejected by
the patient. Further, if bone-marrow progenitors
circulating in the blood could be attracted to sites of
disease, surgery could be avoided.”

www.stemcell-tech.com

Adult cells are behind much of stem cell success so far

The great potential moral controversies and political party
alignments associated with stem cell issue makes the subject
a hot topic.


Human stem cells can be obtained from human embryos,
produced either by in vitro fertilization of human eggs or
cloning via somatic cell nuclear transplant, or adults.

The often stated advantages of embryonic stem cells are 1)
their great promise, 2) their potential to form every cell
type, 3) their rapid proliferation, 4) their lack of
rejection and finally, 5) their usefulness in drug testing
and disease models.

However, from a scientific and medical point of view these
advantages are less clear.

The "great promise" of embryonic cells is often stated by
scientists that either hold key patents or are strongly
supported by biotech companies pursuing embryonic cells
commercially.

Every type of stem cell may be useful for injuries but are
unlikely to cure most diseases, as underlying causes of
uncured diseases are often not known. Stem cells may
alleviate the symptoms for several years but not affect the
disease process. Other areas of research are actively being
studied on disease processes so stem cells are not the
magic silver bullet in diseases.

The "potential of embryonic stem cells to possibly form
every cell type" in the body is amazing but is of little
clinical relevance. As long as a stem/progenitor cell is
capable of forming the cell types needed for a particular
injury or disease, the capability to form every cell type
is a moot point.

Furthermore, there are numerous supporting studies that
stem cells derived from adults have the same potential.
Sources of adult stem cells include the skin, fat, bone
marrow stromal cells, umbilical cord and many other sites
in the body.

The "rapid proliferation of embryonic stem cells" is rather
ironic claim in that the quality cited for the superiority
of embryonic stem cells is actually responsible for causing
serious problems. Rapid growth is not always a desirable
quality, as clearly seen with weeds in a garden or cancer
in the body.

In an animal model of Parkinson's disease, rats injected
with embryonic stem cells showed a slight benefit in about
50% of the rats, but one-fifth of the rats died of brain
tumors caused by the embryonic stem cells.

The "lack of rejection of embryonic stem cells" is a clever
twist of words. It is true that embryonic cells are not
rejected. However, to be useful as a therapy, the cell must
mature into a particular cell type.

When the cell matures, it is recognized by the immune
system as foreign and is rejected. However, it has also
been argued that this is the reason for the great need for
human cloning (somatic cell nuclear transplant) so the
problem of rejection of embryonic stem cell can be avoided.

This field is in its infancy, and only a very few studies
have been done to even demonstrate the feasibility of this
in experimental animals. Pursuing this extreme measure when
the human body is full of stem/progenitor cells that would
not be rejected is one of the most absurd directions ever
observed in the history of science that is supposedly being
promoted to help people.

"Usefulness in drug testing and disease models" is not a
reasonable claim because tissue models and drugs need to be
tested on mature tissue, not embryonic cells. There are
numerous tissue cultures model systems of muscle, skin,
etc., that are routinely used in drug and disease models.

The advantages of stem cells derived from adult stem cells
are virtually unknown to the American public. The most
profitable, not the best, treatment for people is not
surprisingly getting the most publicity.

The greatest advantage of adult stem cells is that it's
usually possible to use a person's own stem cells, which is
the safest stem cell option for people. This avoids the
problems of rejection, disease transmission, chromosomal
abnormalities and uncontrolled growth.

One problem with embryonic stem cells that is rarely
mentioned is that methods have yet to be developed to grow
these cells in a manner that does not induce significant
chromosomal abnormalities.

If one looks at the human clinical trials or research using
experimental animals, the record for adult stem cells
compared to embryonic stem cells is extremely impressive.
In examining only the scientific evidence, one wonders why
the controversy even exists.

Parkinson's disease: When a transplant consists of
embryonic/fetal tissue, the stem/progenitor cells are the
only cells that survive. In two clinical trials using
embryonic/fetal tissue, devastating deterioration at one
year after treatment occurred in about 15% of these
patients that was believed to result from cellular
overgrowth or from rejection of the foreign cells/tissue
derived from embryo or fetus.

These results are in striking contrast to the report on a
patient who received his own adult stem cells, who had
almost full recovery for several years after the
transplant.

In a recent animal study, human embryonic stem cells not
only did not cause improvement in an animal model of
Parkinson's disease but also caused tumor formation.
Another direction of hope for Parkinson's disease is the
use of growth factors.

Diabetes: Diabetes, like Parkinson's disease, is a disease,
so it may not be possible to cure diabetes with any type of
stem cells but only dissipate the symptoms for several
years. Recently, insulin independence was reported in a
person after receiving cells from her mother.

Also encouraging were results found in animal studies that
blocking the autoimmune reaction can reverse diabetes in
mice. There are also several reports that adult stem cells
can develop into insulin-secreting cells.

Spinal cord injury: The comparison of results with adult
and embryonic stem cells is even more dramatic. Although
mice receiving embryonic stem cells made the front page of
many newspapers and extensive web coverage, a paper
published by Zurita and Vaquero found almost total recovery
from complete paralysis in rats using adult stem cells from
bone marrow. Transplants of tissue containing one's own
stem cells is safe and causes some improvement in people
with severe, chronic spinal cord injury.

Heart disease: Several recent studies patients with heart
attacks report benefit from adult stem cells derived from
bone marrow. Clinical trials have also shown improvements
in some patients with heart failure after using one's own
adult stem cells in treatment.

Similar comparisons can be made for a variety of diseases
and injuries. But the successes with adult stem cells will
never make headlines or be heard by the majority of the
American public.

Although it may take years for these adult stem cell
treatments to be commonly available, the results with adult
stem cells will eventually end a controversy that should
never have existed in the first place. The controversy may
end even sooner than that with last month's report of
embryonic stem cells can be derived from sperm, as reported
in the most recent edition of "Nature."

Get More info on how you can benefit from your own Stem Cells
please go here: http://www.stemcell-tech.com

Jean Peduzzi-Nelson is an associate professor in the
department of anatomy and cell biology Wayne State
University School of Medicine in Detroit.

Adult Stem Cells Help Weakened Hearts

Even patients who suffered an episode decades ago can
benefit, researchers say. By Karen Kaplan and Alan Zarembo
Times Staff Writers

September 21, 2006

Using stem cells harvested from patients' own bone marrow,
researchers improved cardiac function in heart attack
patients months, years — and even decades — after the
attacks, they reported Wednesday.

The infusion of stem cells boosted cardiac pumping
efficiency by 7% in three months — a modest gain, but still
a significant improvement for a chronic condition.

In one case, a patient who had suffered a heart attack 30
years earlier showed an 11% improvement after the
treatment, according to the study in the New England
Journal of Medicine.

The German researchers also found tentative signs that
patients could continue to improve with repeated
treatments.

"We have always thought that a heart attack is permanent
damage, but now there is the potential that this damage can
be repaired," said Dr. Christopher P. Cannon, a
cardiologist at Brigham and Women's Hospital in Boston who
was not involved in the research.

Though the researchers are uncertain why the therapy works,
the findings are a sign that the long-touted regenerative
powers of stem cells may be gradually moving from the
laboratory into viable human therapies.

Some researchers cautioned that it was too soon to say that
the results could be translated into a routine treatment.

"There are a number of therapies that have gotten to this
step but when subjected to more rigorous trials have not
worked," said Dr. Gregg C. Fonarow, a professor of
cardiovascular medicine at UCLA.

But Dr. Andreas M. Zeiher, chair of the department of
medicine at Johann Wolfgang Goethe University in Frankfurt
and senior author of the study, said the preliminary
results pointed to potential new strategies for treating
chronic heart disease, for which there is no cure.

Stem cells present one of the most tantalizing mysteries in
medicine. One form, known as embryonic stem cells, are
capable of generating any type of tissue in the body, but
scientists haven't learned the biochemical means to
transform them.

The current study focused on a second type of cells known
as adult stem cells. There are many types, each focused on
regenerating a specific group of tissues to help the body
repair normal wear and tear.

Stem cells from bone marrow have been used for decades to
regenerate blood and immune cells in cancer patients.
Laboratory experiments suggest that these cells also can
make heart muscle, blood vessels, nerve cells and other
tissues.

The advantage of bone marrow stem cells is that they are
easy to extract and can be collected from the same patients
they will be used to treat, avoiding problems of tissue
rejection.

Heart disease has been one of the primary targets of stem
cell research.

One of five deaths in the United States is caused by a
heart attack, which occurs when heart muscle is deprived of
blood and dies. About 1.2 million heart attacks occur in
the United States every year, leading to nearly 500,000
deaths, according to the American Heart Assn.

The German researchers recruited 75 patients who had
suffered a heart attack at least three months — and as long
as 30 years — earlier.

The patients were already receiving state-of-the-art drug
treatments for their heart disease, including the use of
beta blockers and cholesterol-lowering statins.

The researchers extracted 50 milliliters of bone marrow
from the patients' hips. They isolated a soup of cells that
included the stem cells and infused it into patients within
a matter of hours.

The researchers divided the patients into three groups. One
received the bone marrow stem cells and another was treated
with different stem cells derived from their own blood. A
third group served as a control.

Three months later, the researchers tested the patients'
left ventricular ejection fraction, a measure of how much
oxygenated blood is pumped into the circulatory system. In
healthy people, it ranges from 57% to 75%.

The patients in the study started out with ejection
fractions that averaged from 39% to 43%.

Those treated with bone marrow stem cells saw their
heart-pumping efficiency increase over three months by an
average of 2.9 points — a 7% improvement.

Over the same period, patients in the control group saw
their pumping efficiency decline by an average of about 3%,
and those treated with blood stem cells dropped about 1%.

To confirm their findings, the researchers swapped the
treatments and gave patients in the control group either
blood or bone marrow stem cells. Again, the patients who
got bone marrow cells saw an increase in their pumping
efficiency.

Fonarow of UCLA said the improvement was similar to the
effect of statins, which boost pumping efficiency by 5% to
8%.

The patients treated with bone marrow cells showed an
increased ability to tolerate physical activity before
becoming tired or breathless — and the improvements have
been sustained, Zeiher said.

He said one patient who had suffered a heart attack four
years earlier improved by 61% and returned to the golf
course to play at least nine holes.

"For the past 20 years, we have obsessed about treating
[heart attacks] quickly — time is muscle," said Dr. Douglas
Losordo, chief of cardiovascular research at St.
Elizabeth's Medical Center in Boston. "What this paper
tells us is there is another time window for therapeutic
intervention that's quite a bit longer and larger than we
thought."

Dr. Anthony Rosenzweig, director of cardiovascular research
at Beth Israel Deaconess Medical Center in Boston, said the
results suggested the stem cells were doing more than just
accelerating the recovery process.

It had been six years on average since these patients had
their heart attacks, he said. "If it were just hastening
healing after a heart attack, you wouldn't necessarily
predict you'd be able to have a beneficial impact so long
after."

Laboratory experiments have shown the cells can rebuild
damaged heart cells, stimulate the formation of new blood
vessels and release chemicals that aid the healing process,
Zeiher said. Some doctors, however, noted that a key piece
of information was missing from the study: What exactly
were the bone marrow cells doing inside the heart?

"They provide no evidence that the injected [stem cells]
actually settled in the heart," Dr. Robert S. Schwartz,
deputy editor of the New England Journal, wrote in a
perspective piece accompanying the study. He added in an
interview: "Physicians should know how any therapy they
give works. That's fundamental."

Others found the mystery less bothersome.

"We still don't know how statins work, but I haven't
stopped prescribing them," Losordo said.

The German researchers also published results of a
companion study showing that patients who received bone
marrow cells within seven days of a heart attack improved
their blood-pumping efficiency by 11% after four months,
compared with a 6% boost for patients who got a placebo.

A third study, conducted by researchers in Norway, found
their stem cell method provided no improvement, although
the study was not precise enough to detect the small
increases in pumping efficiency reported by the German
team.

Adult Stem Cells May Treat Diabetes

Adult stem cells from human bone marrow may help treat type
2 diabetes.

That’s the early finding from lab tests on diabetic mice.
Tests on people haven’t been done.

The mouse studies are summed up in the Proceedings of the
National Academy of Sciences.

Researchers included biochemistry professor Darwin Prockop,
MD, PhD, who directs Tulane University’s Center for Gene
Therapy.

The researchers studied male mice with high blood sugar
like that in type 2 diabetes.

Half the mice received two injections of adult stem cells
taken from human bone marrow. With their defective immune
systems, the mice didn’t reject the human cells.

For comparison, the other mice didn’t get any injections.

Over the next month or so, mice treated with stem cells
made more insulin, a hormone that controls blood sugar.

Stem cells turned up in the mice’s pancreas, which makes
insulin.

The stem-cell treated mice also had less kidney damage than
mice in the comparison group, the study shows.

Diabetes can cause kidney damage. Stem cells showed up in
the mice’s kidneys as well; the injected cells may have
helped repair damage, the researchers say.

It’s possible, but not yet certain, that stem cell shots
could boost insulin production and help fix damaged tissue
in people with diabetes, according to Prockop’s team.

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