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Stem cells treatments
are a type of cells therapy that introduce new
cells into damaged tissue in order to treat
a disease or injury. Many medical researchers
believe that stem cells treatments have the
potential to change the face of human disease
and alleviate suffering. The ability of stem
cells to self-renew and give rise to subsequent
generations that can differentiate offers a
large potential to culture tissues that can
replace diseased and damaged tissues in the
body, without the risk of rejection.
A number of stem cells treatments exist, although
most are still experimental and/or costly, with
the notable exception of bone marrow transplantation.
Medical researchers anticipate one day being
able to use technologies derived from adult
and embryonic stem cells research to treat cancer,
Type 1 diabetes mellitus, Parkinson's disease,
Huntington's disease, cardiac failure, muscle
damage and neurological disorders, along with
many others.
More research is needed concerning both stem
cells behavior and the mechanisms of the diseases
they could be used to treat before most of these
experimental treatments become realities
Current Stem Cells treatments
For over 30 years, bone marrow, and more recently,
umbilical cord blood stem cells have been used
to treat cancer patients with conditions such
as leukemia and lymphoma. During chemotherapy,
most growing cells are killed by the cytotoxic
agents. These agents not only kill the leukemia
or neoplastic cells, but also the haematopoietic
stem cells within the bone marrow. It is this
side effect of the chemotherapy that the stem
cells transplant attempts to reverse; the donor's
healthy bone marrow reintroduces functional
stem cells to replace those lost in the treatment.
Potential Stem Cells Treatments
Brain damage
Stroke and traumatic brain injury lead to cells
death, characterized by a loss of neurons and
oligodendrocytes within the brain. Healthy adult
brains contain neural stem cells, these divide
and act to maintain general stem cells numbers
or become progenitor cells. In healthy adult
animals, progenitor cells migrate within the
brain and function primarily to maintain neuron
populations for olfaction (the sense of smell).
Interestingly, in pregnancy and after injury,
this system appears to be regulated by growth
factors and can increase the rate at which new
brain matter is formed. In the case of brain
injury, although the reparative process appears
to initiate, substantial recovery is rarely
observed in adults, suggesting a lack of robustness.
Stem cells may also be used to treat brain degeneration,
such as in Parkinson's and Alzheimer's disease.
Cancer
Research injecting neural (adult) stem cells
into the brains of dogs has shown to be very
successful in treating cancerous tumors. With
traditional techniques brain cancer is almost
impossible to treat because it spreads so rapidly.
Researchers at the Harvard Medical School induced
intracranial tumours in rodents. Then, they
injected human neural stem cells. Within days
the cells had migrated into the cancerous area
and produced cytosine deaminase, an enzyme that
converts a non-toxic pro-drug into a chemotheraputic
agent. As a result, the injected substance was
able to reduce tumor mass by 81 percent. The
stem cells neither differentiated nor turned
tumorigenic.[4] Some researchers believe that
the key to finding a cure for cancer is to inhibit
cancer stem cells, where the cancer tumor originates.
Currently, cancer treatments are designed to
kill all cancer cells, but through this method,
researchers would be able to develop drugs to
specifically target these stem cells.
Spinal cord injury
A team of Korean researchers reported on November
25, 2004, that they had transplanted multipotent
adult stem cells from an umbilical cord blood
to a patient suffering from a spinal cord injury
and that she can now walk on her own, without
difficulty. The patient had not been able stand
up for roughly 19 years. For the unprecedented
clinical test, the scientists isolated adult
stem cells from umbilical cord blood and then
injected them into the damaged part of the spinal
cord.
According to the October 7, 2005 issue of The
Week, University of California researchers injected
human embryonic stem cells into paralyzed mice,
which resulted in the mice regaining the ability
to move and walk four months later. The researchers
discovered upon dissecting the mice that the
stem cells regenerated not only the neurons,
but also the cells of the myelin sheath, a layer
of cells which insulates neural impulses and
speeds them up, facilitating communication with
the brain (damage to which is often the cause
of neurological injury in humans).
In January 2005, researchers at the University
of Wisconsin-Madison differentiated human blastocyst
stem cells into neural stem cells, then into
the beginnings of motor neurons, and finally
into spinal motor neuron cells, the cells type
that, in the human body, transmits messages
from the brain to the spinal cord. The newly
generated motor neurons exhibited electrical
activity, the signature action of neurons. Lead
researcher Su-Chun Zhang described the process
as "you need to teach the blastocyst stem
cells to change step by step, where each step
has different conditions and a strict window
of time."
Transforming blastocyst stem cells into motor
neurons had eluded researchers for decades.
The next step will be to test if the newly generated
neurons can communicate with other cells when
transplanted into a living animal; the first
test will be in chicken embryos. Su-Chun said
their trial-and-error study helped them learn
how motor neuron cells, which are key to the
nervous system, develop in the first place.
The new cells could be used to treat diseases
like Lou Gehrig's disease, muscular dystrophy,
and spinal cord injuries.
Heart damage
Several clinical trials targeting heart disease
have shown that adult stem cells therapy is
safe and effective, and is equally efficient
in old as well as recent infarcts. Adult stem
cells therapy for heart disease was commercially
available on at least five continents at the
last count (2007).
Possible mechanisms are:
• Generation of heart muscle cells
• Stimulation of growth of new blood vessels
that repopulate the heart tissue
• Secretion of growth factors, rather than actually
incorporating into the heart
• Assistance via some other mechanism
It may be possible to have adult bone marrow
cells differentiate into heart muscle cells.
Haematopoiesis (blood cells formation)
The specificity of the human immune cells repertoire
is what allows the human body to defend itself
from rapidly adapting antigen. However, this
system it a hot spot for degradation upon the
pathogenesis of disease, and because of the
critical role that it plays in organismal defense,
its degradation is often fatal to the system
as a whole. Diseases of hematopoietic cells
are called hematopathology. The specificity
of one's immune cells repertoire, which allows
it to recognize foreign antigen, causes further
challenges in the treatment of immune disease.
Identical matches between donor and recipient
must be made for successful transplantation
treatments, while matches are uncommon, even
between first-degree relatives. Research using
both hematopoietic adult stem cells and embryonic
stem cells has contributed great insight into
possible mechanisms and methods of treatment
for many of these ailments.
Fully mature human red blood cells may be generated
ex vivo by hematopoietic stem cells (HSCs),
which are precursors of red blood cells. In
this process, HSCs are grown together with stromal
cells, creating an environment that mimics the
conditions of bone marrow, the natural site
of red blood cells growth. Erythropoietin, a
growth factor, is added, coaxing the stem cells
to complete terminal differentiation into red
blood cells. Further research into this technique
should have potential benefits to gene therapy,
blood transfusion, and topical medicine.
Baldness
Hair follicles also contain stem cells, and
some researchers predict research on these follicle
stem cells may lead to successes in treating
baldness through "hair multiplication",
also known as "hair cloning". This
treatment is expected to work through taking
stem cells from existing follicles, multiplying
them in cultures, and implanting the new follicles
into the scalp. Later treatments may be able
to simply signal follicle stem cells to give
off chemical signals to nearby follicle cells
which have shrunk during the aging process,
which in turn respond to these signals by regenerating
and once again making healthy hair.
Missing teeth
In 2004, scientists at King's College London
discovered a way to cultivate a complete tooth
in mice and were able to grow them stand-alone
in the laboratory. Researchers are confident
that this technology can be used to grow live
teeth in human patients.
In theory, stem cells taken from the patient
could be coaxed in the lab into turning into
a tooth bud which, when implanted in the gums,
will give rise to a new tooth, which would be
expected to take two months to grow. It will
fuse with the jawbone and release chemicals
that encourage nerves and blood vessels to connect
with it. The process is similar to what happens
when humans grow their original adult teeth.
Many challenges remain, however, before stem
cells could be a choice for the replacement
of missing teeth in the future.
Deafness
There has been success in re-growing cochlea
hair cells with the use of stem cells.
Blindness and vision impairment
Since 2003, researchers have successfully transplanted
retinal stem cells into damaged eyes to restore
vision. Using embryonic stem cells, scientists
are able to grow a thin sheet of totipotent
stem cells in the laboratory. When these sheets
are transplanted over the damaged retina, the
stem cells stimulate renewed repair, eventually
restoring vision. The latest such development
was in June 2005, when researchers at the Queen
Victoria Hospital of Sussex, England were able
to restore the sight of forty patients using
the same technique. The group, led by Dr. Sheraz
Daya, was able to successfully use adult stem
cells obtained from the patient, a relative,
or even a cadaver. Further rounds of trials
are ongoing.
In April 2005, doctors in the UK transplanted
corneal stem cells from an organ donor to the
cornea of Deborah Catlyn, a woman who was blinded
in one eye when an acid was thrown in her eye
at a nightclub. The cornea, which is the transparent
window of the eye, is a particularly suitable
site for transplants. In fact, the first successful
human transplant was a cornea transplant. The
cornea has the remarkable property that it does
not contain any blood vessels, making it relatively
easy to transplant. The majority of corneal
transplants carried out today are due to a degenerative
disease called keratoconus.
The University Hospital of New Jersey claims
a success rate growing the new cells from transplanted
stem cells varies from 25 percent to 70 percent.
In 2009, researchers at the University of Pittsburgh
Medical center demonstrated that stem cells
collected from human corneas can restore transparency
without provoking a rejection response in mice
with corneal damage.
Amyotrophic lateral sclerosis
Stem cells have cured rats with an Amyotrophic
lateral sclerosis-like disease. The rats were
injected with a virus to kill the spinal cord
motor nerves related to leg movement, succeeded
by injections of stem cells into their spinal
cords. These migrated (passed through many layers
of tissues) to the sites of injury where they
were able to regenerate the dead nerve cells
restoring the rats which were once again able
to walk.
Graft vs. host disease and Crohn's disease
Phase III clinical trials expected to end in
second-quarter 2008 were conducted by Osiris
Therapeutics using their in-development product
Prochymal, derived from adult bone marrow. The
target disorders of this therapeutic are graft-versus-host
disease and Crohn's disease.
Neural and behavioral birth defects
A team of researchers led by Prof. Joseph Yanai
were able to reverse learning deficits in the
offspring of pregnant mice who were exposed
to heroin and the pesticide organophosphate.
This was done by direct neural stem cells transplantation
into the brains of the offspring. The recovery
was almost 100 percent, as proved in behavioral
tests in which the treated animals improved
to normal behavior and learning scores after
the transplantation. On the molecular level,
brain chemistry of the treated animals was also
restored to normal. Through the work, which
was supported by the US National Institutes
of Health, the US-Israel Binational Science
Foundation and the Israel anti-drug authorities,
the researchers discovered that the stem cells
worked even in cases where most of the cells
died out in the host brain.
The scientists found that before they die the
neural stem cells succeed in inducing the host
brain to produce large numbers of stem cells
which repair the damage. These findings, which
answered a major question in the stem cells
research community, were published earlier this
year in the leading journal, Molecular Psychiatry.
Scientists are now developing procedures to
administer the neural stem cells in the least
invasive way possible - probably via blood vessels,
making therapy practical and clinically feasible.
Researchers also plan to work on developing
methods to take cells from the patient's own
body, turn them into stem cells, and then transplant
them back into the patient's blood via the blood
stream. Aside from decreasing the chances of
immunological rejection, the approach will also
eliminate the controversial ethical issues involved
in the use of stem cells from human embryos.
Diabetes
Diabetes patients lose the function of their
insulin-producing beta cells of their pancreas.
Human embryonic stem cells may be grown in cells
culture and stimulated to form insulin-producing
cells that can be transplanted into the patient.
However, success depends on developing procedures
in all required steps:
Have the cells proliferate and generate sufficient
amount of tissue
• Differentiation into the right cells type
• Survival of the cells in the recipient (prevention
of transplant rejection)
• Integration with the surrounding tissue in
the body
• Function appropriately in long-term
Orthopedics
Clinical case reports in the treatment of orthopedic
conditions have been reported. To date, the
focus in the literature for musculoskeletal
care appears to be on mesenchymal stem cells.
Centeno et al. have published MRI evidence of
increased cartilage and meniscus volume in individual
human subjects, though it is unclear how the
MRI results compare to clinical response. However,
each of these articles only describes one lucky
individual and the results of trials including
more patients are yet to be published making
it hard to extrapolate the efficacy and safety.
It has also yet to be shown that these results
apply to a larger group of patients.
Wakitani has also published a small case series
of nine defects in five knees involving surgical
transplantation of mesenchymal stem cells with
coverage of the treated chondral defects.
Wound healing
In one experimental method in regenerative medicine,
stem cells are used to stimulate the growth
of human tissues. In an adult, wounded tissue
is most often replaced by scar tissue, which
is characterized in the skin by disorganized
collagen structure, loss of hair follicles and
irregular vascular structure. In the case of
wounded fetal tissue, however, wounded tissue
is replaced with normal tissue through the activity
of stem cells. A possible method for tissue
regeneration in adults is to place adult stem
cells "seeds" inside a tissue bed
"soil" in a wound bed and allow the
stem cells to stimulate differentiation in the
tissue bed cells. This method elicits a regenerative
response more similar to fetal wound-healing
than adult scar tissue formation. Researchers
are still investigating different aspects of
the "soil" tissue that are conducive
to regeneration.
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