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Unity *Knowledge *Empowerment
Stem Cell Therapy
Introduction to Stem Cell Therapy
Stem cell therapy presents
the potential promise for re-wiring the defective nervous system.
The technology is provocative and promising, but the future is far
from certain. Nevertheless, the science that is unfolding about
neural development is exciting in its potential implications.
Stem Cell research has shown
how environmental cues can control the pace as well as the pathway
of development. Mammalian neurological development is highly
regulated. The fate of each cell is governed by interactions with
its neighbors. For instance, the cells in a half-embryo, or in a
chimeric double embryo, must adjust their behavior so as to generate
an animal that is normal in both pattern and size. When the
circumstances of development are more grossly abnormal, however, the
embryonic cells can go wildly out of control. Some important lessons
can be learned from these phenomena.
If a normal early mouse
embryo is grafted into the kidney or testis of an adult, it rapidly
becomes disorganized, and the normal controls on cell proliferation
break down. The result is a bizarre growth known as a teratoma,
which consists of a disorganized mass of cells containing many
varieties of differentiated tissue - skin, bone, glandular
epithelium, and so on - mixed with undifferentiated stem cells that
continue to divide and generate yet more of these differentiated
tissues.
Teratomas with similar properties can also arise spontaneously from
germ cells in the gonads as the result of various developmental
accidents.
We now know that it is
possible to derive transplantable cancers from teratomas. Such
teratocarcinomas will grow without limit until they kill their host.
They can be maintained indefinitely by grafting samples of the tumor
cells serially from one host to another, and they always include
some undifferentiated stem cells, together with a variety of
differentiated cell types to which the stem cells give rise. The
teratocarcinoma stem cells can also be maintained in culture as
permanent cell lines.
One might think that
teratocarcinoma stem cells originate, as in other cancers, through
mutations in genes responsible for the normal controls of cell
behavior. A number of observations, however, suggest otherwise.
Stem cells with very similar properties can be derived by placing a
normal inner cell mass in culture and dispersing the cells as soon
as they proliferate. Once dispersed, some of the cells, if kept in
suitable culture conditions, will continue dividing indefinitely
without altering their character.
The resulting embryonic stem
(ES) cell lines are similar to teratocarcinoma-derived cell lines,
but they can be generated at such high frequency from normal embryos
that it is unlikely that they arise by mutation. Instead, it appears
that separating the cells from their normal neighbors and placing
them in the appropriate culture medium arrests the normal program of
change of cell character with time, and thus enables the cells to
continue dividing indefinitely without differentiating.
The presence in the medium
of a protein growth factor known as leukemia inhibitory factor (LIF)
seems to be critical for this suspension of developmental progress.
With a slightly more complex cocktail of growth factors, embryonic
germ cells can be induced to behave in the same way in culture.
The state in which the ES,
teratocarcinoma, or germ-cell-derived stem cells are arrested seems
to be equivalent to that of normal inner-cell-mass cells. This can
be shown by taking the cells from their culture dish and injecting
them into the blastocoel cavity of a normal blastocyst. The injected
cells become incorporated in the inner cell mass of the blastocyst
and can contribute to the formation of an apparently normal chimeric
mouse.
Descendants of the injected stem cells can be found in practically
any of the tissues of this mouse. They differentiate in a
well-behaved manner appropriate to their location and can even form
viable germ cells.
This capability of ES cells
forms the basis for a widely used technique that allows mice to be
generated with a genetically engineered mutation in any chosen gene
whose DNA has been cloned. To produce such "gene-knockout" mice,
mutant ES cells are made by selecting for a DNA insertion that
replaces the chosen gene by an artificially altered version; the
mutant ES cells are then used to produce chimeric mice that carry
the mutation in their germ cells.
These extraordinarily
adaptable behaviors of ES cells shows that environmental cues not
only guide choices between different pathways of differentiation,
but in certain cases, they can also stop or start the developmental
clock - the processes that drive a cell to progress from an
embryonic to an adult state.
Brains Can Grow New Cells
In October, 1998, Fred Gage
of the Salk Institute reported that the adult brain was able to grow
new cells in the hippocampus area. Mice research indicates that
neuronal stem cells do indeed migrate to various parts of the mouse
brain in order to grow new neurons. The question for humans is how
to make the neuronal stem cells in the hippocampus area mature in a
healthy manner and migrate to other parts of the brain.
Brain Plasticity
Researchers at the
Massachusetts Institute of Technology have reconfigured newborn
ferret brains so that the animals' eyes are hooked up to brain
regions where hearing normally develops.
The surprising result is that the ferrets develop fully functioning
visual pathways in the auditory portions of their brains. In other
words, they see the world with brain tissue that was only thought
capable of hearing sounds!
These findings run counter
to previous theories of how brains develop specialized regions for
seeing, hearing, sensing touch and - in humans - generating language
and emotional states. Prior theorists argued that genes operating
before birth created these specialized regions or modules. This
meant that the visual cortex was destined to process vision and
little else. The ferret experiments showed that brain regions are
not set in stone at birth. Rather, they develop specialized
functions based on the kind of information flowing into them after birth.
"Some scientists are going
to have a hard time believing these experiments," said Dr. Jon Kaas,
a professor of psychology at Vanderbilt University in Nashville.
They demonstrate î that the cortex can develop in all sorts of
directions. It's just waiting for signals from the environment, and
will wire itself according to the input it gets"
As in humans, the ferret's
optic and auditory nerves travel through the thalamus before
reaching areas in the cerebral cortex where vision and hearing are
perceived. In humans, this very basic wiring is present at birth,
but in ferrets, these important nerves grow into the thalamus after
the animal is born. Dr. Sur found that if he stopped the auditory
nerve from entering the thalamus, the optic nerve would arrive a few
days later and make a double connection. It would go on through the
thalamus and connect itself up to both seeing and hearing regions of
the cortex.
The researchers then waited
to see what would happen to the hearing region of the brain once it
was getting all its signals from the retina.
After a ferret or a human is
born, cells in the brain's primary visual area become highly
specialized for analyzing the orientation of lines found in images
or shapes. Some cells fire only in response to vertical lines
(if
presented with a horizontal or slanted line, they don't do
anything).
Other cells fire exclusively
when a horizontal line falls on them and yet others fire in response
to lines slanted at various angles. These specialized cells are
draped across the primary visual area in a somewhat splotchy fashion
that resembles a bunch of pinwheels.
The hearing region of the
brain is organized very differently. Each cell is connected to the
next in a kind of single line. There are no pinwheel shapes.
After the re-wired ferrets
matured, cells in the auditory cortex were organized pinwheel
fashion. Researchers found horizontal connections between cells
responding to similar orientations.
The re-wired map was less
orderly than the maps found in normal visual cortex, Dr. Sur said,
but looked as if it might be functional.
The researchers then asked,
what does the re-wired ferret experience? Does it see or does it
hear with its auditory cortex? Re-wired ferrets were trained to turn
their heads one way if they heard a sound and in the other direction
if they saw a flash of light. In these experiments, one hemisphere
was re-wired and the other was left normal as a control. Thus the
animals could always hear with the intact side of their brains and
were deaf in the re-wired side.
Not surprisingly, when the
light was presented to the re-wired side, the animals responded
correctly. But when connections to visual areas were severed on the
re-wired side, the animals still responded to the light. That meant
that they were seeing lights with their re-wired auditory cortex,
Dr. Sur said.
The research reopens the
question of what are the relative contributions of genes and
experience in building brain structure, according to Dr. Kaas.
Genes, Dr. Kaas suggests, create a basic scaffold, but not much
structure. Thus, in a normal human brain, the optic nerve is an
inborn scaffold connected to the primary visual area. But it is only
after images pour into this area from the outside world that it
becomes the seeing part of the brain. All the newborn cortex
knows about the outside world comes from the electrical activity of
these inputs, or images that fall on the retina, sounds that reach
the inner ear or touch sensations that press on the skin, Dr. Kaas
said.
As the inputs arrive, the
cells organize themselves into circuits and functional regions. As
these circuits grow larger and more complex, they become less
malleable and - probably with the help of changes in neurochemistry
- become stabilized. This is why a mature brain is less able to
recover from injury than a very young brain.
Young brains are
astonishingly plastic, Dr. Kaas said. For example, children who
suffer from a severe form of epilepsy that is treatable only by
removing one-half of their brains can learn to walk, talk, throw
balls and otherwise develop normally with only half a brain, if
operated on early in life.
But in recent years,
scientists are also discovering that adult brains, as well, can
undergo surprising changes in response to experience. Imaging
experiments carried out on blind people show that when they learn to
read Braille, "visual" areas of their brains light up.
Touch seems also to reside
in visual areas. Similar experiments show that deaf people use the
auditory cortex to read sign language, whereas people who can hear
use the visual areas of the brain for this purpose.
Dr. Sur said his laboratory
was now searching for molecules that help produce these kinds of
changes in mature and developing brains. If the chemistry of
regrowth and reorganization can be understood, he said, it would
offer new avenues for helping people recover from damage caused by
strokes, accidents and various brain diseases
Intravenous Injection of Stem Cells
Still unavailable in the
United States except in the arena of strictly controlled research,
intravenous injections of stem cells are being given in several
clinics elsewhere. Regarding Cerebral Palsy, some of the results
have been favorable - however, to date, only anecdotal and
testimonial data are available. As more scientific reports become
available, we will post them here.
Children's Neurobiological Solutions
Children's
Neurobiological Solutions, Inc. (CNS) is a national, non-profit,
501(c)(3) organization, whose mission is to orchestrate
cutting-edge, collaborative research with the goal of expediting the
creation of effective treatments and therapies for children with
neurodevelopmental abnormalities, birth injuries to the nervous
system, and related neurological problems.
In addition, CNS strives to
provide families and health care providers with user-friendly access
to state-of-the-art information and education supporting their
decision-making processes.
Approximately 15 million
children in the United States, between the ages of 0-19 years, are
afflicted with neurological conditions that severely limit their
quality of life and lifespan.
Special education alone for
these children costs society approximately 36 billion dollars
annually. These costs include more personnel for learning disabled
classes, transportation to out of district placements, out of
district schools for more involved children, equipment, aids, etc.
There are no known cures and
limited biomedical therapeutics. The majority of present and past
research and fundraising dollars focus on saving lives and
supportive services such as physical therapy, special education and
care giving.
Recent advances in
biomedicine, particularly in the fields of developmental
neurobiology, stem cell research and genetics, has opened the
gateway towards the discovery of brain repair therapies which can
enhance mobility and cognition, giving quality of life and health to
these children.
Taking advantage of these
exciting new fields, Children's Neurobiological Solutions has
developed a world-renowned, cross-institutional Scientific Advisory
Board of neuroscientists and clinicians, collaborating to achieve
aggressive research goals. CNS's research goals are focused on the
discovery and development of therapeutics that will improve the
functional abilities and health of these children, enhancing their
quality of life and reducing the burdens of their caretakers and
society.
Articles on Stem Cell
Awaiting the Miracles of Stem-Cell Research
 Stem Cells: A Primer
Neuroscience and Stem Cells: Biological Alchemy
Dr. Evan Snyder: The Man Who Fixes Brains
Stem Cell Research: Scientific, Ethical & Policy Issues
Stem Cell Research: Medical Progress with Responsibility
Teaching the Body to Heal Itself
Human Neurogenesis: Group Demonstrates that Adult Human Brains Grow
New Cells After All
Why Stem Cells Will Transform Medicine
Stem Stem Cells: Brain Surgery for the 21st Century
New Workhorses of Stem Cell Technology: Embryoid Body-derived Cells
Appear to Fulfill Long-sought Combination of Characteristics
A Paradigm Shift in Stem Cell Research?
Stem Cell Researchers Take on Parkinson's: Political Concerns May Be
Holding Up Research into Possibly the Best Cure
Donaldson Report on Stem Cells Released
Stem Cell Research: Coriell Extends Its Scope
Stem Cells: Is This the Mother of All Brain Cells?
News: Cultivating Policy from Cell Types
Stem Cells: The
International Journal of Cell Differentiation and Proliferation
Stem Multilineage Differentiation from Human Embryonic Stem Cell
Lines
"Rainbow" Reporters for Multispectral Marking and Lineage Analysis
of Hematopoietic Stem Cells
New Strategies in the Treatment of Acute Myelogenous Leukemia:
Mobilization and Transplantation of Autologous Peripheral Blood Stem
Cells in Adult Patients
Stem Cells: Dr. Evan Snyder - Closing In On A Cure
More about Evan Y. Snyder, MD, PhD: The Snyder Laboratory
Stem Cell Research Program at the University of Wisconsin, Madison
Embryonic Stem Cell Fact Sheet
Single Shot: The Ability of Stem Cells to Migrate May Mean One
Injection Could Repair Widespread Nerve Damage
Mending Broken Hearts: Simple Cell Implants Could
Undo the Damage Wrought by Heart Attacks
Under Starter's Orders: New Rules Let Researchers in
the US Join the Race to Harness Stem Cells
Everything You Ever Wanted to Know about Stem
Cells
Specific Articles & Research on Stem Cells & Stem Cell Therapy:
-
Awaiting the Miracles of Stem-Cell Research
Hidden in the nooks and crannies of our brains, bone marrow, and
hair follicles are small numbers of nearly immortal cells that
repair damage and constantly rejuvenate our bodies. These
diligent menders, known as adult stem cells because other cells
seem to stem from them, can migrate wherever they are needed and
multiply into armies of new cells to form skin and bone, blood
or brain.
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Stem Cells: A Primer
From the National Institutes of Health
(NIH): This primer
presents background information on stem cells. It includes an
explanation of what stem cells are; what pluripotent stem cells
are; how pluripotent stem cells are derived; why pluripotent
stem cells are important to science; why they hold such great
promise for advances in health care; and what adult stem cells
are.
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Stem Neuroscience and Stem Cells: Biological
Alchemy
From Scientific American Magazine: The discovery that skin and
bone marrow cells can transform into neurons raises hopes - and
many questions. Two years ago Fred H. Gage set neurologists
buzzing when he, his co-workers at the Salk Institute in La
Jolla, Calif., and collaborators in Sweden disproved a
long-standing "fact" that the human brain cannot grow new
neurons once it reaches adulthood. That buzz has recently
intensified into a hum of excitement as new observations of stem
cells - immature cells that can divide repeatedly and give rise
to many different kinds of tissues, including neurons - have
found that the cells appear to be more accessible and more
malleable than scientists had dared hope.
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Dr. Evan Snyder: The Man Who Fixes Brains
Dr. Snyder was the first to isolate and grow these stem cells in
the lab about a decade ago, and, since then, he has rocketed to
prominence on the hope of using them to heal a wide range of
presently incurable brain disorders. Now, for the first time
ever, the traditional view of the brain as an organ where, after
maturity, damaged or dead cells cannot be replaced may be
tottering. "Stem-cell biology is enormously exciting right now
and holds promise for really novel therapies - not just
symptomatic therapies, but maybe cures," says Dr. Gerald
Fischbach, director of the National Institute of Neurological
Disorders and Stroke. Snyder is even bolder, predicting the
first human trials of stem-cell therapy may be only a year or
two away, based on the rapid progress in lab animals. "Before
the decade is out," he said, "there will be some therapeutic
benefits'' from treating disease with neural stem cells.
Parkinson's disease, caused by the death of brain cells in a
certain region, might be one of the first targets for stem-cell
treatment; another is Lou Gehrig's disease, or amyotrophic
lateral sclerosis, because it kills so quickly and there's no
treatment.
-
Stem Cell Research: Scientific, Ethical & Policy
Issues
From the the American Association for the Advancement of Science
and the Institute for Civil Society (AAAS/ICS): In the face of
extraordinary advances in the prevention, diagnosis, and
treatment of human diseases, devastating illnesses such as heart
disease, diabetes, cancer, and diseases of the nervous system,
such as Parkinson's Disease and Alzheimer's Disease, continue to
deprive people of health, independence, and well-being. Research
in human developmental biology has led to the discovery of human
stem cells (precursor cells that can give rise to multiple
tissue types), including embryonic stem
(ES) cells, embryonic
germ (EG) cells, fetal stem cells,
and adult stem cells.
-
Stem Cell Research: Medical Progress with
Responsibility
From the U.S. Department of Health: A report from the Chief
Medical Officer's Expert Group reviewing the potentials of
development in stem cell research and cell nuclear replacement
to benefit human health.
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Teaching the Body to Heal Itself
Dr. Ronald McKay, an expert on neural stem cells at the National
Institutes of Health, believes the body's tissues are
"self-assembling," once their source or stem cells are given the
right cues. "In a few months it will be clear that stem cells
will regenerate tissues," Dr. McKay said. "In two years, people
will routinely be reconstituting liver, regenerating heart,
routinely building pancreatic islets, routinely putting cells
into brain that get incorporated into the normal circuitry. They
will routinely be rebuilding all tissues."
-
Human Neurogenesis: Group Demonstrates that Adult
Human Brains Grow New Cells After All
"Contrary to accepted knowledge, previous evidence existed that
new neurons were born in restricted regions of the adult brain,
but resistance existed that adult neurogenesis was generalizable
to primates and humans. Our results proved that neuro-genesis
does occur in humans," said Fred H. Gage, director of the
Laboratory of Genetics at the Salk Institute for Biological
Studies in La Jolla, Calif., lead investigator for the research.
-
Why Stem Cells Will Transform Medicine
They have the potential to cure disease, regenerate organs, even
prolong life. And they could completely alter the way we
practice medicine. Stem cells are not only entire cells; they
are the exquisitely sensitive cells of early development. They
speak the cellular language fluently, juggling many molecular
messages at once, as they do when building the body. When
transplanted, they appear to respond to molecular cries for
help. They can react to heart-attack damage by forming both
blood vessels and cardiac muscle. They react to neural damage
either by changing into and replacing neurons that have died,
becoming a seamless part of the brain's conversation with
itself, or by issuing molecular instructions, reteaching the
brain the language of rejuvenation. Either way, as Human Genome
Sciences CEO William Haseltine says, stem cells seem to "remind
the body it knows how to heal itself." Harvard neurobiologist
Evan Snyder calls them "magic seeds."
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Stem Stem Cells: Brain Surgery for the 21st
Century
Two years ago Sylvia Elam, a Virginia coal miner's daughter, lay
on an operating table at the University of Pittsburgh Medical
Center. The tiny 65-year-old stroke victim was wrapped like a
mummy, her head attached by four screws to the sides of a metal
box called a stereotactic frame. She was about to become one of
the first 12 patients in history to have neuronal cells, created
in a lab from stem cells, implanted in her brain. Partially
paralyzed by a stroke in 1993, she had watched her life since,
unable to live it, wheelchair-bound at her husband Ira's side.
Her sentences were finished by Ira, who picked out the words
buried in her garbled speech and read her eyes in a face that
was stilled, half by dead brain neurons, half by despair. Two
months later, Elam was walking again. Despite a second stroke,
unrelated to the operation, she says she would like to receive
more cells. Layton Bioscience reported that six of the 12
patients in the initial trial had improved brain activity.
-
New Workhorses of Stem Cell Technology: Embryoid
Body-derived Cells Appear to Fulfill Long-sought Combination of
Characteristics
An interview with John Gearhart, the C. Michael Armstrong
Professor of Obstetrics and Gynecology at the Johns Hopkins
University School of Medicine: Stem cell biology has come full
circle, with one of the two groups that cultured the first human
embryonic stem (ES) cells in 1998 reporting on the isolation of
the most promising type of human stem cell yet: embryoid
body-derived cells, or EBDs. These cells appear to be in a
"ground state," retaining the potential to specialize into
nerve, blood, muscle, or more, yet retaining chromosomal and
cell cycle normalcy - a long sought combination. They can also
be frozen, cloned, and genetically manipulated.
-
A Paradigm Shift in Stem Cell Research?
Stem cell research is upsetting the long-held view that in
animal embryogenesis, position is everything. The idea that a
cell's fate is sealed when it becomes part of endoderm,
mesoderm, or ectoderm--the primary germ layers of the embryo -
was close to gospel. Generations of developmental biologists
meticulously derived "fate maps" tracing the trajectories of
cells in forming embryos. Refuting that notion are recent
observations that brain (ectoderm) can become bone marrow
(mesoderm), that bone marrow can become liver
(endoderm), and
other altered fates not yet published.
-
Stem Cell Researchers Take on Parkinson's:
Political Concerns May Be Holding Up Research into Possibly the
Best Cure
New research shows that by using stem cells, scientists can
produce an unlimited supply of dopamine (DA) neurons, the same
neurons that inexplicably die off in Parkinson's patients.
Scientists at Rockefeller University and Memorial
Sloan-Kettering Cancer Center recently reported that they
produced DA neurons from adult somatic cells using "Dolly-esque"
cloning technology. This finding raises the possibility that one
day, therapeutic cloning could help generate DA neurons from a
patient's own tissue, eliminating the worry that the tissue will
be rejected and freeing transplant patients from having to take
powerful immunosuppressive drugs.
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Donaldson Report on Stem Cells Released
It took Liam Donaldson's expert group a year to decide, but it
delivered a resounding endorsement of stem cell research and its
potential to revolutionise medicine by creating customised
transplants for patients. "My own view, and that of the
committee, is that stem cell research opens up a new medical
frontier," said Donaldson, the chief medical officer. "It's got
major, major medical potential," he declared in London at a
press conference to launch the report. The British government
has accepted in full the expert group's nine recommendations.
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Stem Cell Research: Coriell Extends Its Scope
The small non-profit research facility is set to open a new
umbilical cord blood bank. Cord blood offers a valuable
alternative to bone marrow transplantation for treating
leukemia, and ongoing research suggests that it holds treatment
potential for many other serious diseases, such as cancer. The
institute hopes to investigate trans-differentiation, which is
coaxing stem cells into taking on characteristics of other
tissues. These treated cells then could be used to correct cell
defects that underlie many inborn or acquired diseases. Future
targets could include neurological diseases such as Parkinson's,
central nervous system injuries, muscular dystrophies, cartilage
damaged by arthritis, liver cells damaged by hepatic toxins,
heart cells damaged by myocardial infarctions or virus
infections, according to Dr. Richard D. Huhn.
-
Stem Cells: Is This the Mother of All Brain
Cells?
Cells in the brain that neurologists thought were mere
structural supports could turn out to be the key to future
treatments for degenerative brain diseases. Scientists in Sweden
have shown that ependymal cells do more than simply separate the
fluid that surrounds the brain and spinal cord from neural
tissue. They may, in fact, contain the brain's reserve of stem
cells. Stem cells go on to develop into mature cells, which in
the brain include neurons and various types of supporting cells
called glia. It was long believed that only embryonic brains had
stem cells, which would mean that unlike bones or blood, adult
brains could not regenerate. But in the past few years,
scientists have shown that adult brains can also sprout new
neurons, suggesting that neural stem cells do exist.
-
News: Cultivating Policy from Cell Types
For better or worse, stem cell science has become inextricably
married to stem cell politics. Policymakers who oppose public
financing of embryonic stem cells have used recent adult stem
cell findings to argue for a dismissal of the NIH stem cell
guidelines. The guidelines, finalized last summer during the
Clinton administration, call for funding the use, but not
derivation, of human embryonic stem cells (ESCs); the pro-life
Bush administration appears ready to ban the funding of both.
Yet many stem cell investigators insist that adult stem cell
research does not preclude the need to study human ESCs, and
that investigating both areas will allow for a
cross-fertilization of ideas and techniques.
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Stem Cells: The
International Journal of Cell Differentiation and Proliferation
Stem Cells provides a premier, peer-reviewed
international forum for the publication of original papers and
concise reviews describing basic laboratory investigations of
stem cells and the translation of clinical aspects of their
characterization and manipulation from the lab bench to patient
care. During the free trial period, all users of the Internet
have access to the full content of the journal online. The free
trial period has been extended until further notice
[at least,
until 9/05/01]. The journal covers all aspects of stem cells:
hematopoietic stem cell biology and the role of growth factors;
translational research in blood and marrow transplantation; ex
vivo expansion of PBPC and cord blood; stem cell plasticity;
signal transduction in normal and malignant cells; molecular
mechanisms of leukemogenesis; endothelial-hematopoietic cell
interaction; gene expression and transcription factors.Also
lists many national and international conferences and meetings.
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Stem Multilineage Differentiation from Human
Embryonic Stem Cell Lines
Stem cells are unique cell populations with the ability to
undergo both self-renewal and differentiation. A wide variety of
adult mammalian tissues harbors stem cells, yet "adult" stem
cells may be capable of developing into only a limited number of
cell types. In contrast, embryonic stem (ES) cells, derived from
blastocyst-stage early mammalian embryos, have the ability to
form any fully differentiated cell of the body. Human ES cells
have a normal karyotype, maintain high telomerase activity, and
exhibit remarkable long-term proliferative potential, providing
the possibility for unlimited expansion in culture. Furthermore,
they can differentiate into derivatives of all three embryonic
germ layers when transferred to an in vivo environment. Data are
now emerging that demonstrate human ES cells can initiate
lineage-specific differentiation programs of many tissue and
cell types in vitro. Based on this property, it is likely that
human ES cells will provide a useful differentiation culture
system to study the mechanisms underlying many facets of human
development. Because they have the dual ability to proliferate
indefinitely and differentiate into multiple tissue types, human
ES cells could potentially provide an unlimited supply of tissue
for human transplantation. Though human ES cell-based
transplantation therapy holds great promise to successfully
treat a variety of diseases (e.g., Parkinson's disease,
diabetes, and heart failure) many barriers remain in the way of
successful clinical trials.
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"Rainbow" Reporters for Multispectral Marking and
Lineage Analysis of Hematopoietic Stem Cells
By Teresa S. Hawley, William G. Telford and Robert G. Hawley:
Hematologic diseases potentially benefiting from gene-based
therapies involving hematopoietic stem cells
(HSCs) include
hereditary hemoglobinopathies, immunodeficiency syndromes, and
congenital bleeding disorders such as hemophilia A, as well as
acquired diseases like AIDS. Successful treatment of these blood
diseases with gene-modified HSCs requires high efficiency gene
delivery to the target cell population and persistence of
transgene expression following differentiation. We review flow
cytometric procedures that permit simultaneous, noninvasive
measurements of transgene expression and phenotypic
discrimination of hematopoietic cell subsets.
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New Strategies in the Treatment of Acute
Myelogenous Leukemia: Mobilization and Transplantation of
Autologous Peripheral Blood Stem Cells in Adult Patients
During the last decade high-dose Ara-C
(HIDAC; single doses of 3
g/m2) and autologous stem cell transplantation have been
increasingly used as postremission therapy in adult acute
myelogenous leukemia (AML). Controlled clinical trials have
demonstrated a long-term disease-free survival of 40%-50% for
patients treated with at least two courses of HIDAC. Other
studies have demonstrated that postremission autologous bone
marrow transplantation results in a disease-free survival equal
to or better than conventional chemotherapy. However,
auto-transplantation with mobilized peripheral blood stem cells
(PBSC) would now be preferred instead of autologous bone marrow,
due to the shorter hematopoietic reconstitution period. The
results reviewed in the present article suggest that HIDAC and
autologous PBSC transplantation can be combined in the
postremission treatment of adult AML, and this combination
therapy may also reduce minimal residual disease and the risk of
posttransplant relapse.
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Stem Cells: Dr. Evan Snyder - Closing In On A
Cure
For the victims of incurable brain diseases and their loved
ones, Snyder is a beacon of hope, an optimist in the face of
some of the cruelest afflictions known to humanity. His optimism
and openness to new ways of conducting research has made him a
magnet for support and advocacy groups for diseases from
ataxia-telangietasia, to the rare Canavan syndrome. "Scientists
like Evan Snyder are like first-round draft picks: Every disease
group wants to get their hands on someone like this," said Brad
Margus, of the Florida-based A-T Children's Project. The
excitement about Snyder's work is fueled in part by neural stem
cells' astonishing ability to migrate through the brain, homing
in on nerves that have been damaged and transforming themselves
into specialized nerve cells of the appropriate type.
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More about Evan Y. Snyder, MD, PhD: The Snyder
Laboratory
Dr. Evan Snyder is Assistant Professor of Neurology at the
Harvard Medical School and BostonChildren's Hospital Department
of Neurology (Neuroscience). The use of neural stem cells
(NSCs)
for the study of brain development and plasticity and for gene
therapy and neural repair is the major interest of this
laboratory. Exploring the hypothesis that the NSC provides the
cellular basis for much of the plasticity present in the
mammalian nervous system, we seek to understand the processes by
which murine and human NSCs make their commitment and
differentiation "decisions" during development, degeneration,
and regeneration. The Snyder Laboratory proposes that exploiting
some of the inherent biologic properties of NSCs may provide
novel strategies for redressing CNS dysfunction (the emerging
field of "restorative neurobiology/neurology").
-
Stem Cell Research Program at the University of
Wisconsin, Madison
Interest in stem cell biology has exploded over the last few
years. This is due to the remarkable possibilities they hold
with regard to providing a source of tissues for in vitro
studies, and repairing damaged tissues following disease or
trauma. The mission of this program is to understand the
molecular mechanisms responsible for their proliferation and
differentiation and assess their safety and efficacy following
transplantation.
-
Embryonic Stem Cell Fact Sheet
From the Biological Research Department at the University of
Wisconsin at Madison, this FAQ sheet includes answers to the
following questions: What are embryonic stem cells? Where do
embryonic stem cells come from? Why are they important? How
might they be used to treat disease? Are there other potential
uses for these cells? What can these cells tell us about
development? For instance, screening drugs by testing them on
cultured human embryonic stem cells could help reduce the risk
of drug-related birth defects.
-
Single Shot: The Ability of Stem Cells to Migrate
May Mean One Injection Could Repair Widespread Nerve Damage
Neurobiologists have helped paralysed mice regain the partial
use of their legs: Researchers at John Hopkins University in
Baltimore gave the mice an injection of neural stem cells into
the spine. Stem cells can develop into every type of cell in the
nervous system. Some of the stem cells matured into neurons and
replaced nerve cells that had died off, the researchers found.
Within a few weeks more than half the mice were able to place
both pads of their feet on the floor. Although the mice never
fully regained the ability to walk, the study shows for the
first time that it may be possible to use stem cells to repair
wide spread nerve damage in people. John Gearhart and his
colleagues Jeffrey Rothstein and Douglas Kerr said, "The effect
mimics an inherited neurological disorder in humans known as
spinal motor atrophy, which affects more than 1 in 20,000
infants".
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Mending Broken Hearts: Simple Cell Implants Could
Undo the Damage Wrought by Heart Attacks
Repairing a damaged heart suddenly seems possible. Two teams of
scientists report that stem cells can fix some of the damage
caused by heart attacks. The techniques could be tested in
people as early as next year. A team led by Piero Anversa of New
York Medical College in Valhalla has shown that stem
cells-undifferentiated cells that can give rise to many
specialised types-can repair some of the immediate damage that
is caused by heart attacks.
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Under Starter's Orders: New Rules Let Researchers
in the US Join the Race to Harness Stem Cells
After months of soul-searching, the US National Institutes of
Health has set out guidelines that will allow researchers to
apply for public funds to work with stem cells derived from
human embryos. Publicly funded researchers will at last be able
to join those in industry who are developing ways to grow new
tissue and organs for transplant. Embryonic stem cells are a
type of primordial cell that can be coaxed to grow into any
other type of cell. Many oppose their use because they must
initially be harvested from an embryo, which is inevitably
destroyed in the process. In the US, researchers will not be
allowed to work with human stem cells generated by cloning,
which involves taking genetic material from an adult cell and
putting it in a fertilised egg. Also, public funds will not
support harvesting stem cells from embryos, so researchers will
have to buy them from private labs.
-
Everything You Ever Wanted to Know about Stem
Cells
A quick FAQ primer about stem cells from the
NewScientist,
an excellent on-line source of breaking news, important
research, bio-tech information and ethical concerns regarding
stem cell therapy.
References
Gurdon JB. The
generation of diversity and pattern in animal development. Cell
1992; 68: 185-199.
DiBerardino MA,
Orr NH, McKinnell RG. Feeding tadpoles cloned from Rana
erythrocyte nuclei. PNAS (USA). 1986; 83: 8231-8234.
Gurdon JB.
Transplanted nuclei and cell differentiation. Sci Am 1968;
219(6): 24-35.
McKinnell RG.
Cloning-nuclear transplantation in amphibia. Minneapolis:
University of Minnesota Press, 1978.
Capecchi MR.
The new mouse genetics: altering the genome by gene targeting.
Trends Genet. 1989; 5: 70-76.
Illmensee, K.
Stevens L.C.Teratomas and chimeras. Sci. Am. 1979;
240(4):120-132.
Papaioannou VE,
Gardner RL, McBurney MW, Babinet C, Evans MJ. Participation of
cultured teratocarcinoma cells in mouse embryogenesis. J.Embryol.
Exp. Morphol. 44:93-104, 1978.
Robertson EJ.
Pluripotential stem cell lines as a route into the mouse germ
line. Trends Genet. 2:9-13, 1986.
Williams RL.
Myeloid leukemia inhibitory factor maintains the developmental
potential of embryonic stem cells. Nature 1988; 336:685-687.
Blakeslee S.
'Rewired' Ferrets Overturn Theories of Brain Growth. April
25, 2000 New York Times. See also Sur M., et al. In Nature,
April 20, 2000 issue.
Written and
overseen by
Lewis Mehl-Madrona, M.D., Ph.D.
Program Director, Continuum Center for Health and Healing,
Beth Israel Hospital / Albert Einstein School of Medicine
Credit for this information
goes to Lewis Mehl-Madrona MD PH D and
The
Healing Center Online
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