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, howerver, 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.
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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 grrow 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.
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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 getsî"
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.
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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.
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Childrens Neurobiological Soultions
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.
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Articles & Research on Stem Cells & Stem Cell Therapy
Due to the increasing importance of the rapidly developing field of stem cell research and advances in its potential and practical application, this subsection will be updated regularly to bring you the benefit of this curent knowledge, not only for Cerebral Palsy, but for many other diseases and bio-neurological conditions for which there has previously been no cure and minimal hope of prevention.
Stem cell therapy is still a very controversial, yet amazingly promising area of hope for the amelioration of many tragic diseases and what we now consider as "developmental disorders". We urge you to keep abreast of the advances in this arena, because it is more than likely that it will benefit so many.
Some of the resources and sources of articles listed below may require you to "register" in order to be available to download these very important documents. Please know that such "registration" is absolutely free of charge and usually only requires your entering your email address and perhaps answering a few questions. We strongly urge you to not let this slight inconvenience deter you from accessing these resources. These are very reputable sites - such as Scientific American, Harvard Medical School, The New York Times, Boston Childrens Hospital and the New Scientist Journal, that respect your Internet privacy rights and are used by medical researchers aroubd the world.
Please report any broken or outdated links to our Webmaster.
Also, see our List of Articles & Information on Live Cell and Stem Cell Therapy in the Autism Section of our website.
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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.
- 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.
- 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.
- 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.
- 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."
- 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.
- 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.
- 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.
- 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.
- 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.
- "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.
- 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.
- 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.
- 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".
- 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.
- 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.
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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.
[Return to "Quick-Index" of Stem Cell Therapy for Cerebral Palsy]
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
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