Revolution in Neurology Brain Implant Brings Paralyzed Muscles Back to Life

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— An artificial connection between the brain and muscles can restore complex hand movements in monkeys following paralysis, according to a study funded by the National Institutes of Health.

In a report in the journal Nature,researchers describe how they combined two pieces of technology to create a neuroprosthesis — a device that replaces lost or impaired nervous system function. One piece is a multi-electrode array implanted directly into the brain which serves as a brain-computer interface (BCI). The array allows researchers to detect the activity of about 100 brain cells and decipher the signals that generate arm and hand movements. The second piece is a functional electrical stimulation (FES) device that delivers electrical current to the paralyzed muscles, causing them to contract. The brain array activates the FES device directly, bypassing the spinal cord to allow intentional, brain-controlled muscle contractions and restore movement.

The research team was led by Lee E. Miller, Ph.D., professor of physiology at Northwestern University’s Feinberg School of Medicine in Chicago. Prior to testing the neuroprosthesis, Dr. Miller’s group recorded the brain and muscle activity of two healthy monkeys as the animals performed a task requiring them to reach out, grasp a ball, and release it. The researchers then used the data from the brain-controlled FES device to determine the patterns of muscle activity predicted by the brain activity.

To test the device, the researchers gave monkeys an anesthetic to locally block nerve activity at the elbow, causing temporary paralysis of the hand. With the aid of the neuroprosthesis, both monkeys regained movement in the paralyzed hand, could pick up and move the ball in a nearly routine manner and complete the task as before.

Dr. Miller’s research team also performed grip strength tests, and found that their system restored precision grasping ability. The device allowed voluntary and intentional adjustments in force and grip strength, which are keys to performing everyday tasks naturally and successfully.

This new research moves beyond earlier work from Dr. Miller’s group showing that a similar neuroprosthesis restores monkeys’ ability to flex or extend the wrist despite paralysis. “With these neural engineering methods, we can take some of the important basic physiology that we know about the brain, and use it to connect the brain directly to muscles,” Dr. Miller said. “This connection from brain to muscles might someday be used to help patients paralyzed due to spinal cord injury perform activities of daily living and achieve greater independence.”

In 2008, a team led by Eberhard Fetz, Ph.D. at the University of Washington in Seattle coupled the activity of single neurons to an FES device similar to the one used for Miller’s study. Monkeys learned to activate individual neurons to control the FES device and move a joystick, and could adapt neurons previously unassociated with wrist movement to complete the task. The investigators suggest that this process of learning and adaption plays an important role in how the BCI translates the brain’s activity patterns into adaptive control of the FES device.

The unique design of the ball grasp-and-release task used with the animals in this study is a further contribution to advanced neuroprosthetic testing and development. Daofen Chen, Ph.D., a program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), described how researchers in the field are striving toward devices that will go beyond simple arm movements and allow fine hand and finger movements. “We’ve learned a lot from non-human primate studies focused on 

understanding neural control of arm and wrist movements,” said Dr. Chen. “Dr. Miller’s study builds on those efforts and focuses on the complex hand and finger movements needed to grasp an object.”

FES devices are currently used for foot drop, a clinical condition seen in patients with stroke or partial spinal cord injury where weak or paralyzed muscles cause the toes to catch on the ground while walking, leading to trips and falls. FES can be activated with shoe sensors, or coordinated with walking movements, to stimulate muscles and lift the toes at the appropriate time during a step.

Other FES devices in current clinical use take advantage of the patient’s residual muscle activity. For example, a prosthetic arm can use sensors built into the shoulder, sensing a shrugging motion that is used to stimulate muscles to open or close the hand. However, this is a less precise and less natural method of control, and it is not an option for patients with higher level spinal cord injuries and little or no shoulder and arm movement. For these patients, the creation of a brain-controlled FES device that connects brain activity directly to muscle stimulation would provide an opportunity to restore hand function.

The temporary nerve block used in the current study is a useful model of paralysis, but it does not replicate the chronic changes that occur after prolonged brain and spinal cord injuries, Dr. Miller cautioned. He said the next steps include testing this system in primate models of long-term paralysis, and studying how the brain changes as it continues to use this neuroprosthesis.

The paper was coauthored by researchers Christian Ethier, Ph.D. and Emily Oby at Northwestern University, Chicago and Matt Bauman, now at the University of Pittsburgh. The research was supported by the National Institutes of Health/NINDS (grant #NS053603), the Chicago Community Trust through the Searle Program for Neurological Restoration at the Rehabilitation Institute of Chicago, and the Health Research Fund of Quebec, Canada.

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أفراد من الشرطة يطلقون دفعات من الرصاص ويحاصرون مستشفى المحلة العام

فى تمام الساعة الثامنة صباحا قام بعض افراد من الشرطة باطلاق اعيرة نارية كثيفة  فى الهواء داخل مستشفى المحلة العام مما تسبب فى حالة من الهلع والرعب داخل المستشفى كما قاموا باغلاق جميع مداخل ومخارج المستشفى من الساعة الثامنة صباحا ولمدة 3 ساعات ومنعوا الاطباء والتمريض والمرضى من الدخول او الخروج وذلك احتجاجا على وفاة زميل لهم يدعى/حسن فوزى حسن الذى قتل امس باعيرة نارية وعدم حضور الطبيب الشرعى . علما بان الطبيب الشرعى لايعمل بالمستشفى ويستدعى عند اللزوم لمناظرة الحالات وقد ترتب على ذلك توقف العمل بالمستشفى وفور فك الحصار عن  المستشفى قام العديد من الاطباء والتمريض بمغادرة المستشفى فورا فى حالة من الهلع والرعب

Heart Transplantation Complete Video

On September 19th, 2007 The Department of Cardiothoracic Surgery at the Montefiore-Einstein Heart Center in New York presented an OR-Live.com webcast of a panel discussion on a heart transplant. This procedure was performed on April 17, 2007 by Dr. David D'Alessandro, Cardiothoracic Surgeon at the Center. Dr. Ricardo Bello was the assisting surgeon during the procedure. The panel discussion was moderated by Dr. Daniel Goldstein, Surgical Director of Cardiac Transplantation, Montefiore-Einstein Heart Center. They were joined by a live audience of surgeon-colleagues and cardiologists. The webcast featured video portions of the procedure as well as detailed descriptions of the techniques used.

How Can Human Stem Cells Help to Restore Memory?

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StemCells Inc. hopes a clinical trial of its proprietary stem cells in rodents will lead to a clinical trial with Alzheimer's patients.

Last week, a California biotech company announced that its human stem cells restored memory in rodents bred to have an Alzheimer's-like condition—the first evidence that human neural stem cells can improve memory.

The company, called StemCells, is betting that its proprietary preparation of stem cells from fetal brain tissue will take on many different roles in the central nervous system. The company and its collaborators have already shown that its stem-cell product has potential in protecting vision in diseased eyes, acting as brain support cells, or improving walking ability in rodents with spinal cord injury.

This metamorphic ability is not so surprising—they are stem cells, after all. But experts say the quality of scientists involved in StemCells and the interesting properties of its cells sets the company apart. "They've really been steadfast in their work to get these cells into clinical trials. That is a tough road and they've done it," says Larry Goldstein, a neuronal stem-cell researcher and director of UC San Diego's stem-cell program. 

and has since spent some $200 million improving the technology. "Now we are really in the exciting phase, because now we are looking at human clinical data, as opposed to just small animals," says StemCells CEO Martin McGlynn.

His company is not the only group bringing stem cells into the clinic. While much attention was paid to Geron's departure from the world's first embryonic stem cell trial (see "Geron Shuts Down Pioneering Stem-Cell Program"), many other groups have continued to push their non-embryonic stem-cell therapies forward for leukemia, colitis, stroke, and more. Meanwhile, Advanced Cell Technologycontinues its U.K.-based embryonic stem-cell therapy trials for blindness. Non-embryonic stem cells can come from a variety of sources—bone marrow, blood, as well as donated aborted fetal tissue, as is the case with StemCells and Neuralstem, another company focused on neuronal stem cells. In recent years, scientists have also developed methods for turning normal adult cells into stem cells (so-called induced pluripotent stem cells), but their safety has yet to be tested in humans.

So while StemCells is not a lone wolf, it may well be a pack leader. One of StemCells' first human studies involved a small trial of young children with a rare and fatal neurodegenerative disease called Batten disease. In 2006, the company began the first U.S. Food and Drug Administration-authorized trial of human neural stem cells at Oregon Health and Science University. Through small boreholes in the skull, a neurosurgeon implanted as many as a billion neural stem cells into different locations of the brains of six Batten patients.

The trial has since suggested that the cells are safe and integrate into the brain. At first, the children received immune system-suppressing drugs to prevent their body from rejecting the cells. But after a year, that treatment was stopped. "A big question that we had, that science had, that the FDA had, was what happens to these cells when you withdraw immunosuppression?" says McGlynn.

The treatment, however, did not rescue the children from the effects of the disease, and some have since succumbed to the disorder. Some of the parents of the children who passed away gave permission for an autopsy, enabling the scientists to see that even after one and a half years with no immunosuppression, the transplanted cells had survived. The company wanted to try the cellular therapy in children at an earlier stage of the disease, but was unable to find eligible patients at such a point in the disease course and canceled the trial.

In another small trial, the cells have shown the ability to make functional changes in the human brain. At the University of California, San Francisco, four children with a genetic disease that prevents their brains from producing myelin—the insulating sheath on neurons that is necessary for proper electrical signaling—received the cellular treatment. In StemCells' study, three of the treated boys had small but measureable gains in neurological function, while the fourth remained stable. MRI scans indicate that the boys' neurons have gained more myelin sheaths, which remain even after immunosuppression is removed.

The company has also initiated trials in patients with spinal-cord injuries and macular degeneration, a disease of the eye that gradually destroys central vision. Its Swiss-based trial with spinal-cord injury patients, begun in 2011 at the University of Zurich, has so far enrolled three patients, two of which have reported changes in their sensitivity to touch. These patients each received a direct transplant of 20 million stem cells into the spinal cord. Last month, the company also announced the beginning of a trial for dry age-related macular degeneration, for 

which there are currently no FDA-approved treatments. A trial at the Retina Foundation of the Southwest in Dallas will test stem cells in the eyes of up to 16 patients.

But even with years of solid lab animal data and promising first starts in humans, success is no guarantee. "Animals only tell you a subset," says Goldstein. "Who knows what's going to work for which disease. When you get to clinical trials for people, all bets are off."

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Medical Benefits Of Nanotechnology

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Overview:  Molecular manufacturing (MM) will impact the practice of medicine in many ways. Medicine is highly complex, so it will take some time for the full benefits to be achieved, but many benefits will occur almost immediately. The tools of medicine will become cheaper and more powerful. Research and diagnosis will be far more efficient, allowing rapid response to new diseases, including engineered diseases. Small, cheap, numerous sensors, computers, and other implantable devices may allow continuous health monitoring and semi-automated treatment. Several new kinds of treatment will become possible. As the practice of medicine becomes cheaper and less uncertain, it can become available to more people.

Surgical and diagnostic tools will be elegant and cheap.	Medicine, especially medical research, demands cutting-edge, high-tech tools. These are naturally expensive to manufacture, especially if they must be kept sterile. With a molecular manufacturing system, the cost of production is unrelated to the complexity of the product. Design and testing will still be costly, but once designed, tools can be manufactured in quantity. The incredibly small component size will allow new kinds of tools: for example, a complete surgical robot can be built smaller than a hypodermic needle, and a chemical sensor can be small enough to fit inside a living cell. Because the human body is so complex, accurate knowledge of its state requires gathering large amounts of data. The small size and low cost of nano-built sensors will allow hundreds or thousands of them to be used for routine diagnosis, whereas today only a few data points can be gathered. Integrated sampling and analysis tools will allow real-time monitoring; there will be no need for a separate "lab" to run the tests.
Research and diagnosis will become more efficient.	Medical research has traditionally been a process of trial and error. Make a change, then wait a few hours or days to see its effect on the overall state of health. This required an extremely conservative approach, as medical techniques had to evolve one step at a time. With real-time monitoring of the body's systems, it will be possible to detect undesired effects far earlier, allowing a more aggressive and experimental approach to treatment. Researchers will be able to gather far more data and process it with computers millions of times more powerful. The result will be a detailed model of the body's systems and processes, and the ability to predict the effects of any disease or treatment. Diagnosis will also be far easier and more informative. It will be possible to build thousands of diagnostic tests, including invasive tests and imaging tests, into a single, cheap, hand-held device. A variety of single-molecule detection technologies will be available even with early MM. Trustworthy diagnosis will make medicine far more efficient, and also reduce the risk of malpractice (and thus liability insurance).
Small medical devices can be implanted permanently.	Today, only a few medical devices are implanted permanently. Surgery is always undesirable, and not much functionality can be packed into a device small enough to wear inside the body. Nano-built devices will be far more efficient and compact. As MM technologies gain the ability to synthesize chemicals other than diamond, implantable devices will be able to continuously sense and adjust the body's chemical balance, in the bloodstream or in specific tissues. Even before then, implanted sensors will be valuable in acquiring a continuous record of the person's state of health. This will allow more sensitive adjustment of the body's state, and earlier detection of problems.
More medical problems will be prevented.	Many medical problems are preventable. Some are acquired from the environment, including poisoning, some cancers, and almost all infectious disease. Widespread monitoring of health and the environment will allow detection of the source of such problems before they can injure people. Improved infrastructure such as water filtration will also help to reduce environmentally-acquired disease. Other diseases are related to lifestyle. Current lifestyle advice is difficult to follow and is not always accurate. Better research will greatly improve our understanding of cause and effect, allowing us to live more healthy lifestyles with far less effort. Finally, some problems accumulate over time, and early detection and treatment can correct the problem before it turns into a full-blown disease.
New diseases will be stopped quickly.	New diseases continue to be a threat to the human race. Naturally occurring diseases could be far worse than SARS, and an engineered disease could conceivably wipe out most of the human race. It will be increasingly important to have a technology base that can detect new diseases even before symptoms appear, and create a cure in a matter of days. MM will enable just such a rapid response. With complete genomes and proteomes for humans and for all known pathogens, plus cheap, highly parallel DNA and protein analysis and sufficient computer resources, it will be possible to spot any new pathogen almost immediately. (There is already a project under way to sequence the DNA of every organism in the Sargasso Sea.) Curing a new infectious disease will require some method of detecting and stopping the pathogen. Robert Freitas has described over a dozen nanotechnological ways to disable or destroy pathogens.
Diagnosis and treatment may be semi-automated.	The practice of medicine today involves a lot of uncertainty. Doctors must guess what condition a patient has, and further guess how best to treat it without upsetting the rest of the body's systems. By contrast, when pathogens and chemical imbalances can be directly detected, many conditions will be treatable with no uncertainty, allowing the use of computer-selected treatment in common cases. This may further reduce the cost of medical care, although doctors, regulatory agencies, or the patients themselves may resist the practice initially.
Health will improve and lifespans increase.	Health improvement and life extension do not depend directly on molecular manufacturing, but it will certainly make them accessible to more people. Any treatment that can be automated can be applied to any number of people at low cost. Efficient research will speed the development of cures for complex problems such as cancer and aging. New therapeutic techniques will allow the treatment of more types of diseases.
MM will facilitate genetic therapy.	Genetic therapy holds great promise for treating several serious health problems. However, the current state of the art can also cause problems, including cancer. Eventually, we may hope that MM will be able to directly edit the DNA of living cells in the body. But even without that level of sophistication, massively parallel scanning may enable the sorting of cells modified outside the body. The ability to inject only non-cancerous cells would make some kinds of genetic therapy much safer. Microsurgical techniques could allow the implantation of modified cells directly into the target tissues.
Some organs will be replaceable.	Many organs in the body perform fairly simple functions. Already, sophisticated machinery can replace lung function for hours, heart function for months, and kidney function for years. Since MM can build machines smaller than cells, many other organs will be candidates for replacement or augmentation, including skin, muscles, various digestive organs, and some sensory functions.
Systems can be individually improved.	The body is made of a large number of interacting systems. The blood circulates chemicals all through the body, making each system interdependent with the others. Small, implanted devices will allow the systems to be decoupled and controlled independently to some degree. For example, it may be desirable for the brain to receive more, or less, adrenaline than the muscles. This capability of "heterostasis" may be useful in cases of trauma and disease, or for long-term health maintenance. http://cbproads.com/clickbankstorefront/v4/sf.asp?id=406781

Health Benefits of Fenugreek

Fenugreek is a powerful herb which has been clinically proven to lower high glucose levels in diabetic patients. Fenugreek also promotes heart health and hormone levels.

The seeds of fenugreek (Trigonella foecum-gracum) are commonly used to add flavor to the ethnic dishes of Middle Eastern cuisines. Because of its rich content of alkaloids and natural estrogens, as well as its ability to reduce high blood sugar levels, fenugreek is receiving much attention as a medicinal herb. Recent studies have verified fenugreek's effect on blood sugar, as well as its capacity to restore healthy cholesterol levels, lending credence to the claims of herbal medical traditions, in which fenugreek has been an active player for centuries.

The Top Ten Health Benefits of Fenugreek

Listed here are ten of fenugreek's primary health benefits. This list is by no means exhaustive. As research continues, more uses for this potent herb are likely to be revealed.

Fenugreek and diabetes - In clinical trials, fenugreek seed reduced fasting blood sugar levels in patients with both type 1 (insulin dependent) and type 2 (insulin resistant) diabetes. In an Indian study, diabetic patients were given fenugreek seed powder for a period of ten days. These patients showed significantly reduced fasting blood sugar levels and improved glucose tolerance.

Fenugreek and healthy cholesterol - Diabetic patients studied in the cllinical trials described above also showed significant improvement in blood cholesterol levels. Serum total cholesterol, LDL and VLDL cholesterol and triglycerides were all reduced.

Fenugreek and sexual health - Fenugreek has long been understood to increase libido. The seeds are rich in diogenin, a substance that mimics the activity of estrogen.

Fenugreek and digestion - When fenugreek seeds are eaten, they release mucilage, creating a soothing effect on the digestive organs. This mucilage forms a protective coating on the lining of the stomach and intestine, reducing gastric inflammation, reflux and heartburn.

Fenugreek relieves skin inflammation - Research has shown that fenugreek is an effective topical treatment for skin problems such as abscesses, boils, burns, eczema and gout.

Fenugreek eases childbirth and promotes lactation - Fenugreek has long been believed to stimulate uterine contractions, speeding and easing childbirth. The herb also boosts milk production in nursing mothers.

Fenugreek relieves fever and eases flu symptoms - Fenugreek has traditionally been used to reduce fever and relieve flu symptoms. The seeds are often combined with honey and lemon to make a soothing tea.

Fenugreek eases menopause symptoms - Because of its natural estrogens, fenugreek is effective in treating the symptoms of menopause, including hot flashes, anxiety and

• insomnia.
• Fenugreek may help prevent cancer - Some studies suggest that diogenin, found in fenugreek, may have anti-carcinogenic properties. Fenugreek is also effective as an antioxidant and free radical scavenger.
• Fenugreek is rich in fiber - Fenugreek's rich fiber content make it useful in treating constipation, and as a preventive against cardiovascular disease.

Because it is a food substance, fenugreek may be safely consumed in moderate amounts, either added to food, or in the form of supplements. Along with other powerful herbs and spices, such as cumin, turmeric, cinnamon, black pepper and cayenne pepper, fenugreek is a culinary spice that contributes a wealth of health benefits.

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تمرينات رياضية متنوعة

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RoSS - Robotic Surgical Simulator

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RoSS - Robotic Surgical Simulator , is a training system which uses virtual reality to introduce the user to the fundamentals of robot assisted surgery.

RoSS comes with a comprehensive curriculum to train for motor and cognitive skills required to operate a da Vinci surgical robot.

The similarity of the RoSS console to the master console of the da Vinci® Surgical System has been validated by scientific studies.

January 28, 2012: We are pleased to announce the release of an updated and improved version of the RoSS. The updates include several new software features and hardware options, such as:

• Knot-Tying Module: An industry-first, physics-based knot-tying simulation, is now included.
• Finger Clutch and Pedal Configuration: A new finger clutch and pedal system, matching da Vinci Si® model, is available.
• HoST™ Prostatectomy Procedure Module:  Our novel HoST (Hands-on Surgical Training) technology, which allows novice surgeons to practice robot- assisted surgery in symphony with an expert robotic surgeon, is now available.
• Enhanced Performance Metrics: The RoSS performance measurement system has been enhanced to include additional metrics and plots.

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WHAT IS STEM CELL

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I. Introduction: What are stem cells, and why are they important?

Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

Stem cells are distinguished from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions.

Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. The functions and characteristics of these cells will be explained in this document. Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitrofertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem cell-like state. This new type of stem cell, called induced pluripotent stem cells (iPSCs), will be discussed in a later section of this document.

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lung, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.

Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine.

Laboratory studies of stem cells enable scientists to learn about the cells’ essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.

Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.

II. What are the unique properties of all stem cells?

Stem cells differ from other kinds of cells in the body. All stem cells—regardless of their source—have three general properties: they are capable of dividing and renewing themselves for long periods; they are unspecialized; and they can give rise to specialized cell types.

Stem cells are capable of dividing and renewing themselves for long periods. Unlike muscle cells, blood cells, or nerve cells—which do not normally replicate themselves—stem cells may replicate many times, or proliferate. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.

Scientists are trying to understand two fundamental properties of stem cells that relate to their long-term self-renewal:

1. why can embryonic stem cells proliferate for a year or more in the laboratory without differentiating, but most non-embryonic stem cells cannot; and
2. what are the factors in living organisms that normally regulate stem cellproliferation and self-renewal?

Discovering the answers to these questions may make it possible to understand how cell proliferation is regulated during normal embryonic development or during the abnormal cell division that leads to cancer. Such information would also enable scientists to grow embryonic and non-embryonic stem cells more efficiently in the laboratory.

The specific factors and conditions that allow stem cells to remain unspecialized are of great interest to scientists. It has taken scientists many years of trial and error to learn to derive and maintain stem cells in the laboratory without them spontaneously differentiating into specific cell types. For example, it took two decades to learn how to grow human embryonic stem cells in the laboratory following the development of conditions for growing mouse stem cells. Therefore, understanding the signals in a mature organism that cause a stem cell population to proliferate and remain unspecialized until the cells are needed. Such information is critical for scientists to be able to grow large 

numbers of unspecialized stem cells in the laboratory for further experimentation.

Stem cells are unspecialized. One of the fundamental properties of a stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. For example, a stem cell cannot work with its neighbors to pump blood through the body (like a heart muscle cell), and it cannot carry oxygen molecules through the bloodstream (like a red blood cell). However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells.

Stem cells can give rise to specialized cells. When unspecialized stem cells give rise to specialized cells, the process is called differentiation. While differentiating, the cell usually goes through several stages, becoming more specialized at each step. Scientists are just beginning to understand the signals inside and outside cells that trigger each stem of the differentiation process. The internal signals are controlled by a cell's genes, which are interspersed across long strands of DNA, and carry coded instructions for all cellular structures and functions. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment. The interaction of signals during differentiation causes the cell's DNA to acquire epigenetic marks that restrict DNA expression in the cell and can be passed on through cell division.

Many questions about stem cell differentiation remain. For example, are the internal and external signals for cell differentiation similar for all kinds of stem cells? Can specific sets of signals be identified that promote differentiation into specific cell types? Addressing these questions may lead scientists to find new ways to control stem cell differentiation in the laboratory, thereby growing cells or tissues that can be used for specific purposes such as cell-based therapies or drug screening.

Adult stem cells typically generate the cell types of the tissue in which they reside. For example, a blood-forming adult stem cell in the bone marrow normally gives rise to the many types of blood cells. It is generally accepted that a blood-forming cell in the bone marrow—which is called a hematopoietic stem cell—cannot give rise to the cells of a very different tissue, such as nerve cells in the brain. Experiments over the last several years have purported to show that stem cells from one tissue may give rise to cell types of a completely different tissue. This remains an area of great debate within the research community. This controversy demonstrates the challenges of studying adult stem cells and suggests that additional research using adult stem cells is necessary to understand their full potential as future therapies.

What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized?

There are many ways in which human stem cells can be used in research and the clinic. Studies of human embryonic stem cells will yield information about the complex events that occur during human development. A primary goal of this work is to identify howundifferentiated stem cells become the differentiated cells that form the tissues and organs. Scientists know that turning genes on and off is central to this process. Some of the most serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation. A more complete understanding of the genetic and molecular controls of these processes may yield information about how such diseases arise and suggest new strategies for therapy. Predictably controlling cell proliferation and differentiation requires additional basic research on the molecular and genetic signals that regulate cell division and specialization. While recent developments with iPS cells suggest some of the specific factors that may be involved, techniques must be devised to introduce these factors safely into the cells and control the processes that are induced by these factors.

Human stem cells could also be used to test new drugs. For example, new medications could be tested for safety on differentiated cells generated from human pluripotent cell lines. Other kinds of cell lines are already used in this way. Cancer cell lines, for example, are used to screen potential anti-tumor drugs. The availability of pluripotent stem cells would allow drug testing in a wider range of cell types. However, to screen drugs effectively, the conditions must be identical when comparing different drugs. Therefore, scientists will have to be able to precisely control the differentiation of stem cells into the specific cell type on which drugs will be tested. Current knowledge of the signals controlling differentiation falls short of being able to mimic these conditions precisely to generate pure populations of differentiated cells for each drug being tested.

Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. Today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.

For example, it may become possible to generate healthy heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart disease. Preliminary research in mice and other animals indicates that bone marrow stromal cells, transplanted into a damaged heart, can have beneficial effects. Whether these cells can generate heart muscle cells or stimulate the growth of new blood vessels that repopulate the heart tissue, or help via some other mechanism is actively under investigation. For example, injected cells may accomplish repair by secreting growth factors, rather than actually incorporating into the heart. Promising results from animal studies have served as the basis for a small number of exploratory studies in humans (for discussion, see call-out box, "Can Stem Cells Mend a Broken Heart?"). Other recent studies in cell culturesystems indicate that it may be possible to direct the differentiation of embryonic stem cells or adult bone marrow cells into heart muscle cells (Figure 3).

Can Stem Cells Mend a Broken Heart?: Stem Cells for the Future Treatment of Heart Disease

Cardiovascular disease (CVD), which includes hypertension, coronary heart disease, stroke, and congestive heart failure, has ranked as the number one cause of death in the United States every year since 1900 except 1918, when the nation struggled with an influenza epidemic. Nearly 2600 Americans die of CVD each day, roughly one person every 34 seconds. Given the aging of the population and the relatively dramatic recent increases in the prevalence of cardiovascular risk factors such as obesity and type 2 diabetes, CVD will be a significant health concern well into the 21st century.

Cardiovascular disease can deprive heart tissue of oxygen, thereby killing cardiac muscle cells (cardiomyocytes). This loss triggers a cascade of detrimental events, including formation of scar tissue, an overload of blood flow and pressure capacity, the overstretching of viable cardiac cells attempting to sustain cardiac output, leading to heart failure, and eventual death. Restoring damaged heart muscle tissue, through repair or regeneration, is therefore a potentially new strategy to treat heart failure.

The use of embryonic and adult-derived stem cells for cardiac repair is an active area of research. A number of stem cell types, including embryonic stem (ES) cells, cardiac stem cells that naturally reside within the heart, myoblasts (muscle stem cells), adult bone marrow-derived cells including mesenchymal cells (bone marrow-derived cells that give rise to tissues such as muscle, bone, tendons, ligaments, and adipose tissue), endothelial progenitor cells (cells that give rise to the endothelium, the interior lining of blood vessels), and umbilical cord blood cells, have been investigated as possible sources for regenerating damaged heart tissue. All have been explored in mouse or rat models, and some have been tested in larger animal models, such as pigs.

A few small studies have also been carried out in humans, usually in patients who are undergoing open-heart surgery. Several of these have demonstrated that stem cells that are injected into the circulation or directly into the injured heart tissue appear to improve cardiac function and/or induce the formation of new capillaries. The mechanism for this repair remains controversial, and the stem cells likely regenerate heart tissue through several pathways. However, the stem cell populations that have been tested in these experiments vary widely, as do the conditions of their purification and application. Although much more research is needed to assess the safety and improve the efficacy of this approach, these preliminary clinical experiments show how stem cells may one day be used to repair damaged heart tissue, thereby reducing the burden of cardiovascular disease.

In people who suffer from type 1 diabetes, the cells of the pancreas that normally produce insulin are destroyed by the patient's own immune system. New studies indicate that it may be possible to direct the differentiation of human embryonic stem cells in cell culture to form insulin-producing cells that eventually could be used in transplantation therapy for persons with diabetes.

To realize the promise of novel cell-based therapies for such pervasive and debilitating diseases, scientists must be able to manipulate stem cells so that they possess the necessary characteristics for successful differentiation, transplantation, and engraftment. The following is a list of steps in successful cell-based treatments that scientists will have to learn to control to bring such treatments to the clinic. To be useful for transplant purposes, stem cells must be reproducibly made to:

• Proliferate extensively and generate sufficient quantities of tissue.
• Differentiate into the desired cell type(s).
• Survive in the recipient after transplant.
• Integrate into the surrounding tissue after transplant.
• Function appropriately for the duration of the recipient's life.
• Avoid harming the recipient in any way.

Also, to avoid the problem of immune rejection, scientists are experimenting with different research strategies to generate tissues that will not be rejected.

To summarize, stem cells offer exciting promise for future therapies, but significant technical hurdles remain that will only be overcome through years of intensive research.

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