Five million people in the U.S. suffer with heart failure, resulting in ~60,000 deaths/year at a cost of $30 billion/year. Heart failure occurs when the heart is damaged and becomes unable to meet the demands placed on it. Unlike other organs, the heart is unable to fully repair itself after injury. One of the common causes for the development of heart damage is a heart attack. After a myocardial infarction (heart attack), irreversible loss of contracting heart muscle cells occurs, resulting in scar formation and subsequently heart failure. Current therapies designed to treat heart attack patients in the acute setting include medical therapies and catheter-based technologies that aim to open the blocked coronary arteries with the hope of salvaging as much of the jeopardized heart muscle cells as possible. Unfortunately, despite advances over the past 2 decades, it is rarely possible to rescue the at-risk heart muscle cells from some degree of irreversible injury and death.

Attention has turned to new methods of treating heart attack and heart failure patients in both the acute and chronic settings after their event. Heart transplantation remains the ultimate approach to treating end-stage heart failure patients but this therapy is invasive, costly, some patients are not candidates for transplantation given their other co-morbidities, and most importantly, there are not enough organs for transplanting the increasing number of patients who need this therapy. As such, newer therapies are needed to treat the millions of patients with debilitating heart conditions. Recently, it has been discovered that stem cells may hold therapeutic potential for these patients. Experimental studies in animals have revealed encouraging results when pluripotent stem cells are introduced into the heart around areas of myocardial infarction. These therapies appear to result in improvement in the contractile function of the heart.

However, numerous questions remain unanswered concerning the use of pluripotent stem cells as therapy for patients with heart attack and heart failure. Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells grow and divide indefinitely while maintaining the potential to develop into many tissues of the body, including heart muscle. They provide an unprecedented opportunity to both study human heart muscle in culture in the laboratory, and advance the possibility of their use in therapy for damaged heart muscle. We have developed methods for identifying and isolating specific types of human ES and iPS cells, stimulating them to become human heart muscle cells, and delivering these into the hearts of rodents that have had a heart attack. This research will refine and advance such approaches in small and large animals, develop clinical grade cells for use, and ultimately initiate clinical trials for patients suffering from heart disease.

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Pluripotent Stem CellBased Therapy for Heart Disease ...

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This project aims to demonstrate both safety and efficacy of a heart-derived cell product in patients who have experienced a heart attack either recently or in the past by conducting a mid-stage (Phase II) clinical trial. The cell product is manufactured using heart tissue obtained from a healthy donor and can be used in most other individuals. Its effect is thought to be long-lasting (months-years) although it is expected to be cleared from the body relatively quickly (weeks-months). Treatment is administered during a single brief procedure, requiring a local anesthetic and insertion of a tube (or catheter) into the heart. The overriding goal for the product is to prevent patients who have had a heart attack from deteriorating over time and developing heart failure, a condition which is defined by the hearts inability to pump blood efficiently and one which affects millions of Americans. At the outset of the project, a Phase I trial was underway. The Phase II trial was initiated at the beginning of the current reporting period, and all subjects enrolled in Phase I completed follow up during the current reporting period. Fourteen patients were treated with the heart-derived cell product as part of Phase I. The safety endpoint for the trial was pre-defined and took into consideration the following: inflammation in the heart accompanied by an immune response, death due to abnormal heart rhythms, sudden death, repeat heart attack, treatment for symptoms of heart failure, need for a heart assist device, and need for a heart transplant. Both an independent Data and Safety Monitoring Board (DSMB) and CIRM agreed that Phase I met its safety endpoint. Preliminary efficacy data from Phase I collected during the current reporting period showed evidence of improvements in scar size, a measure of damage in the heart, and ejection fraction, a measure of the hearts ability to pump blood. At the end of the current reporting period, Phase II is still enrolling subjects and clinical trial sites are still being brought on for participation in the trial. Meanwhile, the manufacturing processes established continue to be employed to create cell products for use in Phase II. Manufacturing data and trial status updates were also provided to the Food and Drug Administration (FDA) as part of standard annual reporting.

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Allogeneic Cardiac-Derived Stem Cells for Patients ...

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Engineered human stem cells have been used to enable paraplegic rats to walk independently and regain sensory perception. The implanted rats had some healing in their spinal cords.

Led by Dr. Shulamit Levenberg, of the Technion-Israel Institute of Technology, the researchers implanted human stem cells into rats with a complete spinal cord transection. The stem cells, which were derived from the membrane lining of the mouth, were induced to differentiate into support cells that secrete factors for neural growth and survival.

The work involved more than simply inserting stem cells at various intervals along the spinal cord. The research team also built a three-dimensional scaffold that provided an environment in which the stem cells could attach, grow and differentiate into support cells. This engineered tissue was also seeded with human thrombin and fibrinogen, which served to stabilize and support neurons in the rats spinal cord.

5 of 12 rats (42%) treated with the induced constructs demonstrated BBB scores exceeding 17, a compiled reflection of improved coordinated gait, plantar placement, weight support, recovery of toe clearance, trunk stability, and predominant parallel paw and tail position, suggesting regained cortical motor control.

The induced constructs promoted remarkable recovery in 42% of the rats, and show no efficacy in the remainder of the rats within the same group. This binary effect compels further investigation, since understanding of the underlying mechanisms causing substantial improvement in some animals and no practical improvement in others can render this method into an effective treatment.

Spinal cord injury (SCI), involving damaged axons and glial scar tissue, often culminates in irreversible impairments. Achieving substantial recovery following complete spinal cord transection remains an unmet challenge. Here, we report of implantation of an engineered 3D construct embedded with human oral mucosa stem cells (hOMSC) induced to secrete neuroprotective, immunomodulatory, and axonal elongation-associated factors, in a complete spinal cord transection rat model. Rats implanted with induced tissue engineering constructs regained fine motor control, coordination and walking pattern in sharp contrast to the untreated group that remained paralyzed (42 vs. 0%). Immunofluorescence, CLARITY, MRI, and electrophysiological assessments demonstrated a reconnection bridging the injured area, as well as presence of increased number of myelinated axons, neural precursors, and reduced glial scar tissue in recovered animals treated with the induced cell-embedded constructs. Finally, this construct is made of bio-compatible, clinically approved materials and utilizes a safe and easily extractable cell population. The results warrant further research with regards to the effectiveness of this treatment in addressing spinal cord injury.

Frontiers in Neuroscience Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection.

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Engineered Stem Cells repaired spinal cords in 5 out of 12 ...

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Certain diseases and treatments can deplete a child's healthy stem cells. Sometimes the body needs help to replenish those cells. When this happens, your child may require a very complex process called a stem cell or bone marrow transplant.

Since 1986, Cook Children's Bone Marrow and Stem Cell Transplant program has performed more than 1,000 transplants in children with cancer, blood disorders or inherited conditions. That's what makes this program one of the more diverse and experienced pediatric transplant programs in the Southwest.

Cook Children's is a member of:

Over the last three years, 30 to 40 transplants were performed every year for a variety of diseases, with leukemia being the most common primary diagnosis.

The goal of the program is to provide a stem cell or marrow transplant to any child who needs one and to improve the outcomes for these patients who do not have better therapy options. We work to achieve this goal through excellent clinical care from several services within Cook Children's, quality initiatives and ongoing comparison of our processes and performance against large academic transplant centers and international data.

Common referral diagnoses:

Stem cells are cells in the body that have the potential to turn into anything, such as a skin cell, a liver cell, a brain cell, or a blood cell. Stem cells that turn into blood cells are called hematopoietic stem cells. These cells are capable of developing into the three types of blood cells:

Stem cells may come from the patient or from a donor. Stem cells that come from a patient may come from their own cord blood cells if they were harvested from the mother's placenta immediately after the child was born and frozen for later use. Stem cells may also be harvested and frozen before the child or teen undergoes treatment. These stem cells are thawed and put back into the patient's body after treatment is complete.

Donor stem cells come from a compatible family member or through a match from a national registry of donors. Depending on the particular needs of your child, one or all three types of a donor's stem cells will be harvested:

While all three types can replenish a patient's blood and bone marrow cells, there are advantages and disadvantages to each. The doctor will discuss these issues and suggest the best type of stem cell for your child's illness.

If your child has been diagnosed, you probably have lots of questions. We can help. If you would like to schedule an appointment, refer a patient or speak to our staff, please call our offices at 682-885-4007.

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Bone Marrow and Stem Cell Transplant | Cook Children's

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As their name suggests, embryonic stem cells (ESCs) are stem cells that are derived from embryos. If we wanted to be more scientific, we would say that ESCs are pluripotent stem cells derived from a blastocyst, an embryo in a very early stage (4-5 days of age).A blastocyst is consisted of 50-150 cells. ESCs measure approximately 14m in diameter.

The use of human embryonic stem cells is highly controversial, as their extraction requires the destruction of a human embryo, raising a great number of ethical issues. The main one is whether a blastocyst can be considered a living person or not. Check our article, Stem Cell Controversy for more info on this topic

Embryonic Stem cell propertiesThere are two important attributes that distinguish stem cells from any other typical cell:

Embryonic stem cells are pluripotent, having the capacity to differentiate and develop into almost all kinds of cells belonging to thethree primary germ layers:

As for self-renewal, ES cells have the capacity to replicate indefinitely. In other words they have the ability, under the proper conditions, to produce infinite numbers of daughter cells just from one or a few father cells.

Human Embryonic Stem Cell Extraction And CultureFirst the inner cell mass (ICM) of the blastocyst is separated from the trophectoderm. Then the cells of the ICM are placed on aplastic laboratory culture dish that contains a nutrient broth called the "culture medium".Typically the inner surface of the dish is coated with what is called a "feeder layer", consisting of reprogrammed embryonic mouse skin cells that don't divide. These mouse cells lay in the bottom of the dish and act as a support for the hESCs. The feeder layer not only provides support, but it also releases all the needed nutrients for thehESCs to grow and replicate. Recently, scientists have devised new ways for culturing hESCs without the need of a mouse feeder cell, a really important advance as there is always the danger of viruses being transmitted from the mouse cells to the human embryonic stem cells.

It should be noted that the process described above isn't always successful, and many times the cells fail to replicate and/or survive. If on the other hand, the hESCs do manage to survive and multiply enough so that the dish is "full", they have to be removed and plated into several dishes. This replating and subculturing process can be done again and again for many months. This way we can get millions and millions of hESCs from the handful ones we had at the beginning.

At any stage of the process, a batch of hESCs can be frozen for future use or to be sent somewhere else for further culturing and experimentation.

How are human embryonic stem cells induced to differentiate ?There are various options for researchers to choose from, if they decide to differentiate the cultured cells.

The easiest one, is to simply allow the cells to replicate until the disc is "full". Once the disc is full, they start to clump together forming embryoid bodies(rounded collections of cells ). These embryoid bodies contain all kinds of cells including muscle, nerve, blood and heart cells. As said before, although this is easiest method to induce differentiation, it is the most inefficient and unpredictable as well.

In order to induce differentiation to a specific type of cell, researchers have to change the environment of the dish by employingone of the ways below:

Human Embryonic Stem Cells, potential usesMany researchers believe that studying hESCs is crucial for fully understanding the complex events happening during the fetal development. This knowledge would also include all the complex mechanisms that trigger undifferentiated stem cells to develop into tissues and organs. A deeper understanding of all these mechanisms would in return give scientists a deeper understanding of what sometimes goes wrong and as a result tumours,birth defects and other genetic conditions occur, thus helping them to come up with effective treatments.

Several new studies also address the fact that human embryonicstem cells can be used as models for human genetic disorders that currently have no reliable model system. Two examples are the Fragile-X syndromeandCystic fibrosis.

As of now, there has been only one human clinical trial ,involving embryonic stem cells, with the officialapproval of the U.S. Food and Drug Administration (FDA).The trial started on January 23, 2009, and involved the transplantation ofoligodendrocytes (a cell type of the brain and spinal cord) derived from human embryonic stem cells. During phase I of the trial, 8 to 10paraplegics with fresh spinal cord injuries (two weeks or less) were supposed to participate.

In August 2009,the trial wasput on hold, due to concerns made by the FDA, regarding a small number of microscopic cysts found in several treated rat models. InJuly 30, 2010 the hold was lifted and researchers enrolled the first patient and administered him with the stem cell therapy.

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Embryonic Stem Cells | Stem Cells Freak

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Mesenchymal stem cells (MSCs) are found in the bone marrow and are responsible for bone and cartilage repair. On top of that, they can also produce fat cells. Early research suggesting that MSCs could differentiate into many other cell types and that they could also be obtained from a wide variety of tissues other than bone marrow have not been confirmed. There is still considerable scientific debate surrounding the exact nature of the cells (which are also termed Mesenchymal stem cells) obtained from these other tissues.

As of now, no treatments using mesenchymal stem cells are proven to be effective. There are, however, some clinical trials investigating the safety and effectiveness of MSC treatments for repairing bone or cartilage. Other trials are investigating whether MSCs might help repair blood vessel damage linked to heart attacks or diseases such as critical limb ischaemia, but it is not yet clear whether these treatments will be effective.

Several other features of MSCs, such as their potential effect on immune responses in the body to reduce inflammation to help treat transplant rejection or autoimmune diseases are still under thorough investigation. It will take numerous studies to evaluate their therapeutic value in the future.

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Stem Cell Therapy & Treatment - Diseases and Conditions

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Overview

A bone marrow transplant is a procedure that infuses healthy blood stem cells into your body to replace your damaged or diseased bone marrow. A bone marrow transplant is also called a stem cell transplant.

A bone marrow transplant may be necessary if your bone marrow stops working and doesn't produce enough healthy blood cells.

Bone marrow transplants may use cells from your own body (autologous transplant) or from a donor (allogeneic transplant).

Mayo Clinic's approach

A bone marrow transplant may be used to:

Bone marrow transplants can benefit people with a variety of both cancerous (malignant) and noncancerous (benign) diseases, including:

Bone marrow is the spongy tissue inside some bones. Its job is to produce blood cells. If your bone marrow isn't functioning properly because of cancer or another disease, you may receive a stem cell transplant.

To prepare for a stem cell transplant, you receive chemotherapy to kill the diseased cells and malfunctioning bone marrow. Then, transplanted blood stem cells are put into your bloodstream. The transplanted stem cells find their way to your marrow, where ideally they begin producing new, healthy blood cells.

A bone marrow transplant poses many risks of complications, some potentially fatal.

The risk can depend on many factors, including the type of disease or condition, the type of transplant, and the age and health of the person receiving the transplant.

Although some people experience minimal problems with a bone marrow transplant, others may develop complications that may require treatment or hospitalization. Some complications could even be life-threatening.

Complications that can arise with a bone marrow transplant include:

Your doctor can explain your risk of complications from a bone marrow transplant. Together you can weigh the risks and benefits to decide whether a bone marrow transplant is right for you.

If you receive a transplant that uses stem cells from a donor (allogeneic transplant), you may be at risk of developing graft-versus-host disease (GVHD). This condition occurs when the donor stem cells that make up your new immune system see your body's tissues and organs as something foreign and attack them.

Many people who have an allogeneic transplant get GVHD at some point. The risk of GVHD is a bit greater if the stem cells come from an unrelated donor, but it can happen to anyone who gets a bone marrow transplant from a donor.

GVHD may happen at any time after your transplant. However, it's more common after your bone marrow has started to make healthy cells.

There are two kinds of GVHD: acute and chronic. Acute GVHD usually happens earlier, during the first months after your transplant. It typically affects your skin, digestive tract or liver. Chronic GVHD typically develops later and can affect many organs.

Chronic GVHD signs and symptoms include:

You'll undergo a series of tests and procedures to assess your general health and the status of your condition, and to ensure that you're physically prepared for the transplant. The evaluation may take several days or more.

In addition, a surgeon or radiologist will implant a long thin tube (intravenous catheter) into a large vein in your chest or neck. The catheter, often called a central line, usually remains in place for the duration of your treatment. Your transplant team will use the central line to infuse the transplanted stem cells and other medications and blood products into your body.

If a transplant using your own stem cells (autologous transplant) is planned, you'll undergo a procedure called apheresis (af-uh-REE-sis) to collect blood stem cells.

Before apheresis, you'll receive daily injections of growth factor to increase stem cell production and move stem cells into your circulating blood so that they can be collected.

During apheresis, blood is drawn from a vein and circulated through a machine. The machine separates your blood into different parts, including stem cells. These stem cells are collected and frozen for future use in the transplant. The remaining blood is returned to your body.

If a transplant using stem cells from a donor (allogeneic transplant) is planned, you will need a donor. When you have a donor, stem cells are gathered from that person for the transplant. This process is often called a stem cell harvest or bone marrow harvest. Stem cells can come from your donor's blood or bone marrow. Your transplant team decides which is better for you based on your situation.

Another type of allogeneic transplant uses stem cells from the blood of umbilical cords (cord blood transplant). Mothers can choose to donate umbilical cords after their babies' births. The blood from these cords is frozen and stored in a cord blood bank until needed for a bone marrow transplant.

After you complete your pretransplant tests and procedures, you begin a process known as conditioning. During conditioning, you'll undergo chemotherapy and possibly radiation to:

The type of conditioning process you receive depends on a number of factors, including your disease, overall health and the type of transplant planned. You may have both chemotherapy and radiation or just one of these treatments as part of your conditioning treatment.

Side effects of the conditioning process can include:

You may be able to take medications or other measures to reduce such side effects.

Based on your age and health history, your doctor may recommend lower doses or different types of chemotherapy or radiation for your conditioning treatment. This is called reduced-intensity conditioning.

Reduced-intensity conditioning kills some cancer cells and somewhat suppresses your immune system. Then, the donor's cells are infused into your body. Donor cells replace cells in your bone marrow over time. Immune factors in the donor cells may then fight your cancer cells.

Your bone marrow transplant occurs after you complete the conditioning process. On the day of your transplant, called day zero, stem cells are infused into your body through your central line.

The transplant infusion is painless. You are awake during the procedure.

The transplanted stem cells make their way to your bone marrow, where they begin creating new blood cells. It can take a few weeks for new blood cells to be produced and for your blood counts to begin recovering.

Bone marrow or blood stem cells that have been frozen and thawed contain a preservative that protects the cells. Just before the transplant, you may receive medications to reduce the side effects the preservative may cause. You'll also likely be given IV fluids (hydration) before and after your transplant to help rid your body of the preservative.

Side effects of the preservative may include:

Not everyone experiences side effects from the preservative, and for some people those side effects are minimal.

When the new stem cells enter your body, they begin to travel through your body and to your bone marrow. In time, they multiply and begin to make new, healthy blood cells. This is called engraftment. It usually takes several weeks before the number of blood cells in your body starts to return to normal. In some people, it may take longer.

In the days and weeks after your bone marrow transplant, you'll have blood tests and other tests to monitor your condition. You may need medicine to manage complications, such as nausea and diarrhea.

After your bone marrow transplant, you'll remain under close medical care. If you're experiencing infections or other complications, you may need to stay in the hospital for several days or sometimes longer. Depending on the type of transplant and the risk of complications, you'll need to remain near the hospital for several weeks to months to allow close monitoring.

You may also need periodic transfusions of red blood cells and platelets until your bone marrow begins producing enough of those cells on its own.

You may be at greater risk of infections or other complications for months to years after your transplant.

A bone marrow transplant can cure some diseases and put others into remission. Goals of a bone marrow transplant depend on your individual situation, but usually include controlling or curing your disease, extending your life, and improving your quality of life.

Some people complete bone marrow transplantation with few side effects and complications. Others experience numerous challenging problems, both short and long term. The severity of side effects and the success of the transplant vary from person to person and sometimes can be difficult to predict before the transplant.

It can be discouraging if significant challenges arise during the transplant process. However, it is sometimes helpful to remember that there are many survivors who also experienced some very difficult days during the transplant process but ultimately had successful transplants and have returned to normal activities with a good quality of life.

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this disease.

Living with a bone marrow transplant or waiting for a bone marrow transplant can be difficult, and it's normal to have fears and concerns.

Having support from your friends and family can be helpful. Also, you and your family may benefit from joining a support group of people who understand what you're going through and who can provide support. Support groups offer a place for you and your family to share fears, concerns, difficulties and successes with people who have had similar experiences. You may meet people who have already had a transplant or who are waiting for a transplant.

To learn about transplant support groups in your community, ask your transplant team or social worker for information. Also, several support groups are offered at Mayo Clinic in Arizona, Florida and Minnesota.

Mayo Clinic researchers study medications and treatments for people who have had bone marrow transplants, including new medications to help you stay healthy after your bone marrow transplant.

If your bone marrow transplant is using stem cells from a donor (allogeneic transplant), you may be at risk of graft-versus-host disease. This condition occurs when a donor's transplanted stem cells attack the recipient's body. Doctors may prescribe medications to help prevent graft-versus-host disease and reduce your immune system's reaction (immunosuppressive medications).

After your transplant, it will take time for your immune system to recover. You may be given antibiotics to prevent infections. You may also be prescribed antifungal, antibacterial or antiviral medications. Doctors continue to study and develop several new medications, including new antifungal medications, antibacterial medications, antiviral medications and immunosuppressive medications.

After your bone marrow transplant, you may need to adjust your diet to stay healthy and to prevent excessive weight gain. Maintaining a healthy weight can help prevent high blood pressure, high cholesterol and other negative health effects.

Your nutrition specialist (dietitian) and other members of your transplant team will work with you to create a healthy-eating plan that meets your needs and complements your lifestyle. Your dietitian may also give you food suggestions to control side effects of chemotherapy and radiation, such as nausea.

Your dietitian will also provide you with healthy food options and ideas to use in your eating plan. Your dietitian's recommendations may include:

After your bone marrow transplant, you may make exercise and physical activity a regular part of your life to continue to improve your health and fitness. Exercising regularly helps you control your weight, strengthen your bones, increase your endurance, strengthen your muscles and keep your heart healthy.

Your treatment team may work with you to set up a routine exercise program to meet your needs. You may perform exercises daily, such as walking and other activities. As you recover, you can slowly increase your physical activity.

Oct. 13, 2016

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Bone marrow transplant - About - Mayo Clinic

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Overview

A spinal cord injury damage to any part of the spinal cord or nerves at the end of the spinal canal (cauda equina) often causes permanent changes in strength, sensation and other body functions below the site of the injury.

If you've recently experienced a spinal cord injury, it might seem like every aspect of your life has been affected. You might feel the effects of your injury mentally, emotionally and socially.

Many scientists are optimistic that advances in research will someday make the repair of spinal cord injuries possible. Research studies are ongoing around the world. In the meantime, treatments and rehabilitation allow many people with spinal cord injuries to lead productive, independent lives.

Your ability to control your limbs after a spinal cord injury depends on two factors: the place of the injury along your spinal cord and the severity of injury to the spinal cord.

The lowest normal part of your spinal cord is referred to as the neurological level of your injury. The severity of the injury is often called "the completeness" and is classified as either of the following:

Additionally, paralysis from a spinal cord injury may be referred to as:

Your health care team will perform a series of tests to determine the neurological level and completeness of your injury.

Spinal cord injuries of any kind may result in one or more of the following signs and symptoms:

Emergency signs and symptoms of a spinal cord injury after an accident may include:

Anyone who experiences significant trauma to his or her head or neck needs immediate medical evaluation for the possibility of a spinal injury. In fact, it's safest to assume that trauma victims have a spinal injury until proved otherwise because:

Spinal cord injuries may result from damage to the vertebrae, ligaments or disks of the spinal column or to the spinal cord itself.

A traumatic spinal cord injury may stem from a sudden, traumatic blow to your spine that fractures, dislocates, crushes or compresses one or more of your vertebrae. It also may result from a gunshot or knife wound that penetrates and cuts your spinal cord.

Additional damage usually occurs over days or weeks because of bleeding, swelling, inflammation and fluid accumulation in and around your spinal cord.

A nontraumatic spinal cord injury may be caused by arthritis, cancer, inflammation, infections or disk degeneration of the spine.

The central nervous system comprises the brain and spinal cord. The spinal cord, made of soft tissue and surrounded by bones (vertebrae), extends downward from the base of your brain and is made up of nerve cells and groups of nerves called tracts, which go to different parts of your body.

The lower end of your spinal cord stops a little above your waist in the region called the conus medullaris. Below this region is a group of nerve roots called the cauda equina.

Tracts in your spinal cord carry messages between the brain and the rest of the body. Motor tracts carry signals from the brain to control muscle movement. Sensory tracts carry signals from body parts to the brain relating to heat, cold, pressure, pain and the position of your limbs.

Whether the cause is traumatic or nontraumatic, the damage affects the nerve fibers passing through the injured area and may impair part or all of your corresponding muscles and nerves below the injury site.

A chest (thoracic) or lower back (lumbar) injury can affect your torso, legs, bowel and bladder control, and sexual function. A neck (cervical) injury affects the same areas in addition to affecting movements of your arms and, possibly, your ability to breathe.

The most common causes of spinal cord injuries in the United States are:

Although a spinal cord injury is usually the result of an accident and can happen to anyone, certain factors may predispose you to a higher risk of sustaining a spinal cord injury, including:

At first, changes in the way your body functions may be overwhelming. However, your rehabilitation team will help you develop the tools you need to address the changes caused by the spinal cord injury, in addition to recommending equipment and resources to promote quality of life and independence. Areas often affected include:

Bladder control. Your bladder will continue to store urine from your kidneys. However, your brain may not be able to control your bladder as well because the message carrier (the spinal cord) has been injured.

The changes in bladder control increase your risk of urinary tract infections. The changes also may cause kidney infections and kidney or bladder stones. During rehabilitation, you'll learn new techniques to help empty your bladder.

Skin sensation. Below the neurological level of your injury, you may have lost part of or all skin sensations. Therefore, your skin can't send a message to your brain when it's injured by certain things such as prolonged pressure, heat or cold.

This can make you more susceptible to pressure sores, but changing positions frequently with help, if needed can help prevent these sores. You'll learn proper skin care during rehabilitation, which can help you avoid these problems.

Circulatory control. A spinal cord injury may cause circulatory problems ranging from low blood pressure when you rise (orthostatic hypotension) to swelling of your extremities. These circulation changes may also increase your risk of developing blood clots, such as deep vein thrombosis or a pulmonary embolus.

Another problem with circulatory control is a potentially life-threatening rise in blood pressure (autonomic hyperreflexia). Your rehabilitation team will teach you how to address these problems if they affect you.

Respiratory system. Your injury may make it more difficult to breathe and cough if your abdominal and chest muscles are affected. These include the diaphragm and the muscles in your chest wall and abdomen.

Your neurological level of injury will determine what kind of breathing problems you may have. If you have a cervical and thoracic spinal cord injury, you may have an increased risk of pneumonia or other lung problems. Medications and therapy can help prevent and treat these problems.

Fitness and wellness. Weight loss and muscle atrophy are common soon after a spinal cord injury. Limited mobility may lead to a more sedentary lifestyle, placing you at risk of obesity, cardiovascular disease and diabetes.

A dietitian can help you eat a nutritious diet to sustain an adequate weight. Physical and occupational therapists can help you develop a fitness and exercise program.

Following this advice may reduce your risk of a spinal cord injury:

Drive safely. Car crashes are one of the most common causes of spinal cord injuries. Wear a seat belt every time you drive or ride in a car.

Make sure that your children wear a seat belt or use an age- and weight-appropriate child safety seat. To protect them from air bag injuries, children under age 12 should always ride in the back seat.

Dec. 19, 2017

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Spinal cord injury - Symptoms and causes - Mayo Clinic

Spinal Cord Stem Cells Comments Off on Spinal cord injury – Symptoms and causes – Mayo Clinic | December 21st, 2017

When the healthy stem cells come from you, the procedure is called an autologous transplant. When the stem cells come from another person, called a donor, it is an allogeneic transplant. Blood or bone marrow transplants most commonly are used to treat blood cancers or other kinds of blood diseases that decrease the number of healthy blood cells in the body. These transplants also may be used to treat other disorders.

For allogeneic transplants, your doctor will try to find a donor whose blood cells are the best match for you. Your doctor will consider using cells from your close family members, from people who are not related to you and who have registered with the National Marrow Donor Program, or from publicly stored umbilical cord blood. Although it is best to find a donor who is an exact match to you, new transplant procedures are making it possible to use donors who are not an exact match.

Blood or bone marrow transplants are usually performed in a hospital. Often, you must stay in the hospital for one to two weeks before the transplant to prepare. During this time, you will have a narrow tube placed in one of your large veins. You may be given medicine to make you sleepy for this procedure. You also will receive special medicines and possibly radiation to destroy your abnormal stem cells and to weaken your immune system so that it wont reject the donor cells after the transplant.

On the day of the transplant, you will be awake and may get medicine to relax you during the procedure. The stem cells will be given to you through the narrow tube in your vein. The stem cells will travel through your blood to your bone marrow, where they will begin making new healthy blood cells.

After the transplant, your doctor will check your blood counts every day to see if new blood cells have started to grow in your bone marrow. Depending on the type of transplant, you may be able to leave, but stay near the hospital, or you may need to remain in the hospital for weeks or months. The length of time will depend on how your immune system is recovering and whether or not the transplanted cells stay in your body. Before you leave the hospital, the doctors will give you detailed instructions that you must follow to prevent infection and other complications. Your doctor will keep monitoring your recovery, possibly for up to oneyear.

Although blood or bone marrow transplant is an effective treatment for some conditions, the procedure can cause early or late complications. The required medicines and radiation can cause nausea, vomiting, diarrhea, tiredness, mouth sores, skin rashes, hair loss, or liver damage. These treatments also can weaken your immune system and increase your risk for infection. Some people may experience a serious complication called graft-versus-host disease if the donated stem cells attack the body. Other people may reject the donor stem cells after the transplant, which can be an extremely serious complication.

VisitBlood-Forming Stem Cell Transplantsfor more information about this topic.

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Blood and Bone Marrow Transplant - NHLBI, NIH

Bone Marrow Stem Cells Comments Off on Blood and Bone Marrow Transplant – NHLBI, NIH | December 19th, 2017

Epidermolysis bullosais is rare, but the charity DEBRA, which campaigns for EB patients, estimates half a million people are affected around the world.

There are different forms of epidermolysis bullosa, including simplex, dystrophic and, as in this case, junctional.

Each is caused by different genetic faults leading to different building blocks of skin being missing.

Prof Michele De Luca, from the University of Modena and Reggio Emilia, told the BBC: The gene is different, the protein is different and the outcome may be different [for each form of EB] so we need formal clinical trials.

But if they can make it work, it could be a therapy that lasts a lifetime.

An analysis of the structure of the skin of the first patient to get 80% of his replaced has discovered a group of long-lived stem cells are that constantly renewing his genetically modified skin.

Genetically modified skin cells were grown to make skin grafts totalling 0.85 sq m (9 sq ft). It took three operations over that winter to cover 80% of the childs body in the new skin. But 21 months later, the skin is functioning normally with no sign of blistering.

Nature Regeneration of the entire human epidermis using transgenic stem cells

Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin cancer. Here we show that autologous transgenic keratinocyte cultures regenerated an entire, fully functional epidermis on a seven-year-old child suffering from a devastating, life-threatening form of JEB. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection. Clonal tracing showed that the human epidermis is sustained not by equipotent progenitors, but by a limited number of long-lived stem cells, detected as holoclones, that can extensively self-renew in vitro and in vivo and produce progenitors that replenish terminally differentiated keratinocytes. This study provides a blueprint that can be applied to other stem cell-mediated combined ex vivo cell and gene therapies

SOURCES BBC News, Nature

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Skin Stem Cells Comments Off on Regeneration of the entire human skin using transgenic … | December 13th, 2017

If theres one thing skin can do well, its grow. Each month our body replaces its skin,nearly 19 million skin cells per inch a feat thats been far less successful in the lab. However, the days of lab-grown skin may not be too far off:Recently, a team of Japanese scientists not only grew fully functional skin tissue, but also transplanted it successfully onto living organisms.

Though the technique has only been tested on mice so far, the team predicts it could one day revolutionize treatments for burn victims, or other patients that have suffered catastrophic skin damage. On a less gruesome note, the team says it may also be useful in treating a more common condition: baldness.

The study, published online in Science Advances, involved researchers from the Riken Center for Developmental Biology and Tokyo University of Science, among other Japanese institutions. The researchers first step was to transform cells from the gums of mice into induced pluripotent stem cells, or adult cells that have been genetically reprogrammed back into an embryonic stem cell state. This is done by forcing the cells to express genes associated with embryonic stem cells. Once transformed into stem cells, they can then be manipulated to become any type of cell in the body.

Next, the team placed the stem cells into a petri dish, where they added the molecule Wnt10b, which coaxed the stem cells to form into clusters that resembled a developing embryo. These clusters were then transplanted into mice bred without a fully functional immune system, which ensured that their bodies did not reject the transplant. Here, they underwent cell differentiation, the process by which unspecialized cells become specialized. In this case, they were becoming skin cells, and once the process had begun, the cells were transplanted again onto the skin of new mice, where they made normal connections with surrounding nerve and muscle tissue to become fully functional skin.

Skin is one of the largest and most important organs in the human body, yet its also one of the most difficult to treat when its damaged. Current treatment options involve painful skin grafts or barely functional artificial skin. According to the new study, however, being able to grow skin in the lab will account for more than just skin's use in protecting our inner bodies. The lab-grown skin also showed the ability to develop hair follicles and sweat glands, which play a role in controlling body temperature and keeping the skin moisturized it's in these areas that skin repair has often fallen short.

"Up until now, artificial skin development has been hampered by the fact that the skin lacked the important organs, such as hair follicles and exocrine glands, lead researcher, Takashi Tsuji of the RIKEN Center for Developmental Biology,said in a recent statement. With this new technique, we have successfully grown skin that replicates the function of normal tissue.

In addition to revolutionizing skin repair, the technique may also help those with certain types of hair loss. The study noted that using Wnet10b on the stem cells resulted in the production of a higher number of hair follicles than previous attempts at growing skin. Within two weeks of receiving the transplanted skin, the mice began to grow hair. Dr. Seth Orlow, chair of dermatology at NYU School of Medicine in New York City, told U.S. News Health that this feature of the lab-grown skin could be manipulated to help patients with both alopecia and pattern baldness.

In theory, we may eventually be able to create structures like hair follicles and other skin glands that could be transplanted back to people who need them, Orlow told U.S. Health News.

According to The Washington Post, the technique is still about five to 10 years away from being safe and effective enough to be used on humans. But with about 95 percent of men and 50 percent of women experiencing some degree of baldness over the course of their lives, its a safe bet that there will be no shortage of eager customers ready to get their hair back when the treatment is approved for use in doctors offices.

Source: Takagi R, Ishimaru J, Sugawara A, et al. Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model. Science Advances . 2016

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Fully Functional Skin Grown From Stem Cells Could Double ...

Skin Stem Cells Comments Off on Fully Functional Skin Grown From Stem Cells Could Double … | December 13th, 2017

To meet the industry needs and to benefit students and research scholars, Nitte University has set up the a centre for stem cell research at K S Hedge Medical Academy (Kshema).

The Nitte University Centre for Stem Cell Research and Regenerative Medicine (NUCSReM), has been established to further advance the understanding of stem cell biology and to facilitate clinical application of stem cells to treat patients with various ailments, says N Vinaya Hegde, chancellor, Nitte University.

Gianvito Martino, the head of the Neurosciences division at the Institute of San Raffaele in Milan in a speech at Multiple Sclerosis Week, which took place from May 23-31, warned against trips of hope to clinics that promise effective treatments using stem cells.

According to Martino, who coordinated a Consensus Conference on last Tuesday in London on the neurodegenerative disease, where the guidelines for pre-clinical studies and clinical treatments with stem cells were defined, hundreds of Italian patients each year go on these trips due to cures that are promised. In the best-case scenario, these patients return in the Read More

Scientists have claimed they would serve the worlds first test tube hamburger this October.

A team, led by Prof Mark Post of Maastricht University in the Netherlands, says it has already grown artificial meat in the laboratory, and now aims to create a hamburger, identical to a real stuff, by generating strips of meat from stem cells.

The finished product is expected to cost nearly 220,000 pounds, The Daily Telegraph reported.

Prof Post said his team has successfully replicated the process with cow cells and calf serum, bringing the first artificial burger a step closer.

In October we are going to provide a Read More

Studies begun by Harvard Stem Cell Institute (HSCI) scientists eight years ago have led to a report published today that may be amount to a major step in developing treatments for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrigs disease.

The findings by Kevin Eggan, a professor in Harvards Department of Stem Cell and Regenerative Biology (HSCRB), and colleagues also has produced functionally identical results in human motor neurons in a laboratory dish and in a mouse model of the disease, demonstrating that modeling the human disease with customized stem cells in the laboratory could relatively soon eliminate some Read More

Frank LaFerla, left, Mathew Blurton-Jones and colleagues found that neural stem cells could be a potential treatment for advanced Alzheimer's disease

UC Irvine scientists have shown for the first time that neural stem cells can rescue memory in mice with advanced Alzheimers disease, raising hopes of a potential treatment for the leading cause of elderly dementia that afflicts 5.3 million people in the U.S.

Mice genetically engineered to have Alzheimers performed markedly better on memory tests a month after mouse neural stem cells were injected into their brains. The stem cells secreted a protein that created more neural connections, improving Read More

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"Latest Stem Cells News" - news from the world about stem ...

Cardiac Stem Cells Comments Off on "Latest Stem Cells News" – news from the world about stem … | November 26th, 2017

Stem cell research is often controversial but it has also led to incredible medical progress in recent years.

Stem cell research is at defining moment. Although it can be controversial and does raise a lot of important ethical issues, this area of medical science has been characterised by a number of important advances, ever since the first embryonic stem cells were isolated from mice in the 1980s. In the near future, it could reshape the way we treat some of the worlds most debilitating diseases.

Stem cells have already been used as treatment for a number of years think bone marrow transplant and they have the potential to help with many other medical conditions. They could also prove crucial for scientists wishing to understand more about human biology and development.

Studies using stem cells have benefited from important media coverage in recent years and many of them hailed as breakthroughs. However, the reality is often more complex, and a number of scientific and ethical challenges often stand in the way of successes in animal models being replicated in humans.

IBTimes UK takes a look at what stem cell research is, what it is used for and what the future looks like.

Stem cells could be defined as building block cells that have not yet differentiated into one cell type and could develop into many different cell types. Stem cells can continue to divide almost indenitely.

There are two main types of stem cells: embryonic stem cells and adult stem cells.

Embryonic stem cells were first isolated in mice in the early 1980s at the University of Cambridge. All developing embryos contains a number of stem cells that can go on to develop into different cell types. In humans, these cells can be isolated from around five days after the egg has been fertilised around 50 to 100 stem cells are present at that stage.

These cells are isolated from embryos that have been donated by couples who have been through IVF and have extra embryos left which were not used during the treatment.

Stem cells are also found in adults, particularly in the bone marrow, the blood, the eyes, the brain and the muscles. They are also known as somatic stem cells.

They can also differentiate into other cells, but into a much more limited number than embryonic stem cells. They range from cells that are able to form different kinds of tissues to more specialised cells that form just some of the cells of a particular tissue or organ. They also have the ability to divide and reproduce indefinitely.

19th Place: Dr Gist F Croft, Lauren Pietilla, Stephanie Tse, Dr. Szilvia Galgoczi, Maria Fenner, Dr Ali H. Brivanlou, Rockefeller University, Brivanlou Laboratory New York, New York, USA: Human neural rosette primordial brain cells, differentiated from embryonic stem cells Confocal, 10x (Dr Gist F Croft, Lauren Pietilla, Stephanie Tse, Dr. Szilvia Galgoczi, Maria Fenner, Dr Ali H. Brivanlou)

Scientists have also found a way to make induced pluripotent stem cells cells taken from any adult tissue and genetically modified to behave like an embryonic stem cell (and thus able to differentiate into any cell type). The term pluripotant refers to the fact that the stem cells can produce almost all of the cells in the body.

To create these induced pluripotent stem cells, researchershave learnt to reprogramme the genes of human adult cells. A major 2007 US study, found that introducing 14 genes could reprogramme the cells to become stem cells, and the researchers then narrowed this down to four genes. Subsequent studies have built on this knowledge to find new, safer ways to turn adult cells into pluripotant stem cells.

Stem cells are already used to help a number of patients around the world. For nearly 50 years, they have been used in the form of bone marrow transplants.

Indeed, bone marrow contains stem cells that can produce many different blood cells. A bone marrow transplant can be used to treat people with blood cancers or genetic blood disorders, such as sickle cell anaemia. The stem cell turn into healthy blood cells that can help the patient. Some hospitals also use stem cells to grow skin grafts for patients with life-threatening burns. It is also possible to receive a stem cell therapy based on limbal stem cells (in the eye) to repair damaged corneas.

Stem cells are also very useful for scientists conducting basic research on diseases, as they can be used to model a large number of conditions. Recent studies have used stem cells to model the nerve cells that are lost in Alzheimers disease or to model deafness or Autism Spectrum disorder.

Scientists have gained a better understanding of blood stem cells (Alden Chadwick/Flickr)

A number of treatment using stem cells has been tested by researchers around the world. A type of patients that could be helped by stems cells are those suffering from spinal cord injuries. Stem cell therapy for spinal cord repair could be used to promote the growth of nerve cells directly or to transplant cells that protect the nerves and help them function.

One of most important studies in this area was published in October 2010. tested the used embryonic stem cells on patients in the US who had sustained a spinal cord injury in the previous 14 days. Preliminary findings were encouraging.

Studies have also been conducted to assess the safety and efficacy of stem cells in helping patients who suffered a stroke. The idea is that stem cells could help in rehabilitation after a persons brain has been damaged by the stroke. Stem cells have also been investigated to treat diseases such as MS, diabetes and to reverse ageing.

Beyond clinical trials, which still remain limited in number, many of the preliminary research opens up a number of very interesting perspectives. One of the main area of interest is growing organs in the lab from tissues created from stem cells. These organs may one day be used for transplantation in humans.

Recently, stem cells have been shown to present an interest to improve fertility treatments with the creation of a new technique in mice in-vitro gametogenesis. The idea is to create eggs and sperm using pluripotant stem cells.

By La Surugue

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What are stem cells and how will they be used to treat the ...

Spinal Cord Stem Cells Comments Off on What are stem cells and how will they be used to treat the … | November 25th, 2017

acute myelogenous leukemia

(uh-KYOOT my-uh-LAH-juh-nuss loo-KEE-mee-uh) A cancer of the blood cells. It happens when very young white blood cells (blasts) in the bone marrow fail to mature. The blast cells stay in the bone marrow and become to numerous. This slows production of red blood cells and platelets. Some cases of MDS become AML. But most do not. Also called AML, acute myeloblastic leukemia, acute myelocytic leukemia, acute myeloid leukemia.

A procedure where bone marrow stem cells are taken from a genetically matched donor (a brother, sister, or unrelated donor) and given to the patient through an intravenous (IV) line. In time, donated stem cells start making new, healthy blood cells.

See complementary and alternative medicine.

(an-uh-fuh-LAK-suss) A very severe allergic reaction to a foreign protein, as in a bee sting, or to a medicine. This reaction causes the blood pressure to drop and trouble breathing. Before a patient receives ATG, a treatment for aplastic anemia, a skin test is given to find out if they are likely to develop anaphylaxis. Also known as anaphylactic shock.

An approach to treating bone marrow failure using natural male hormones. Androgen therapy can help the bone marrow make more blood cells. This is an older treatment for bone marrow failure that is rarely used because of the side effects. Scientists are studying these medicines to try to better understand why they work in some cases of acquired and genetic bone marrow failure.

(uh-NEE-mee-uh) A condition in which there is a shortage of red blood cells in the bloodstream. This causes a low red blood cell count. Symptoms of anemia are fatigue and tiredness.

(an-tee-by-AH-tik) A medicine that fights bacterial infections. When a person with bone marrow failure does not have enough neutrophils, the white blood cells that fight infection, antibiotics may help to prevent and fight infection.

(ant-i-ko-AG-yuh-lunt) See blood thinner.

(ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells: red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most scientists believe that aplastic anemia happens when the immune system attacks the bone marrow stem cells. Aplastic anemia can be acquired (begin any time in life) or can be hereditary (less common, passed down from parent to child).

Programmed cell death.

(uh-SITE-eez) Extra fluid and swelling in the belly area (abdomen). Also called hydroperitoneum.

Any condition that happens when the immune system attacks the body's own normal tissues by mistake.

A procedure in which some of the patient's own bone marrow stem cells are removed, frozen, and then returned to the through an intravenous (IV) line. In time, the stem cells start making new, healthy blood cells.

Describes one of several ways that a trait or disorder can be inherited, or passed down through families. "Autosomal" means that the mutated, or abnormal, gene is located on one of the numbered, or non-sex, chromosomes. "Dominant" means that only one copy of the mutated gene is enough to cause the disease. Dyskeratosis congenita is a rare cause of bone marrow failure disease. It may have an autosomal dominant, autosomal recessive or x-linked pattern of inheritance.

Describes one of several ways that a trait or disorder can be inherited, or passed down through families. "Autosomal" means that the mutated, or abnormal, gene is located on one of the numbered, or non-sex, chromosomes. "Recessive" means that two copies of a mutated gene must be present to cause the disease. Dyskeratosis congenita is a rare cause of bone marrow failure. It may have an autosomal dominant, autosomal recessive or x-linked pattern of inheritance.

The study of a subject to increase knowledge and understanding about it. The goal of basic research in medicine is to better understand disease. In the laboratory, basic research scientists study changes in cells and molecules linked to disease. Basic research helps lead to better ways of diagnosing, treating, and preventing disease. Also called basic science research.

A type of white blood cell that plays a role in allergic reactions.

A chemical that is widely used by the chemical industry in the United States to make plastics, resins, nylon and synthetic fibers. Benzene is found in tobacco smoke, vehicle emissions, and gasoline fumes. Exposure to benzene may increase the risk of developing a bone marrow failure disease. Benzene can affect human health by causing bone marrow stem cells not to work correctly.

(bil-i-ROO-bun) A reddish yellow substance formed when red blood cells break apart. It is found in the bile and in the blood. Yellowing of the skin and eyes can occur with high levels of bilirubin. Also called total bilirubin.

A substance made from a living system, such as a virus, and used to prevent or treat disease. Biological drugs include antibodies, globulin, interleukins, serum, and vaccines. Also called a biologic or biological drug.

A young white blood cell. The number of blast cells in the bone marrow helps define how severe MDS is in a person. When 20 out of 100 cells in the bone marrow are blasts, this is considered acute myeloid leukemia.

See Blast Cells.

A mass of blood that forms when platelets stick together. Harmful blood clots are more likely to happen in PNH. The term thrombus describes a blood clot that develops and attaches to a blood vessel. The term embolus describes a blood clot or other foreign matter that gets into the bloodstream and gets stuck in a blood vessel.

A medicine used to stop blood clots from forming. Blood thinners can be used to treat or prevent clots. Some common blood thinners are enoxaprin (Lovenox), heparin (Calciparine or Liquaemin), and warfarin (Coumadin). Also called and anticoagulant or thrombopoiesis inhibitor.

A procedure in which whole blood or one of its components is given to a person through an intravenous (IV) line into the bloodstream. A red blood cell transfusion or a platelet transfuson can help some patients with low blood counts.

The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow.

A medical procedure to remove of a small amount of liquid bone marrow through a needle inserted into the back of the hip. The liquid bone marrow is examined for abnormalities in cell size, shape, or look. Tests may also be run on the bone marrow cells to look for any genetic abnormalities.

A medical procedure to remove a small piece of solid bone marrow using a needle that goes into the marrow of the hip bone. The solid bone marrow is examined for cell abnormalities, the number of different cells and checked for scaring of the bone marrow.

A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be hereditary (less common, passed down from parent to child).

A procedure where bone marrow stem cells are collected from marrow inside the donor's hipbone and given to the patient through an intravenous (IV) line. In time, donated stem cells start making new, healthy blood cells.

(bud-kee-AR-ee SIN-drome) A blood clot in the major vein that leaves the liver (hepatic vein). The liver and the spleen may become enlarged. Budd-Chiari syndrome can occur in PNH.

How much of the bone marrow volume is occupied by various types of blood cells.

(kee-moe-THER-uh-pee) The use of medicines that kill cells (cytotoxic agents). People with high-risk or intermediate-2 risk myelodysplastic syndrome (MDS) may be given chemotherapy to kill bone marrow cells that have an abnormal size, shape, or look. Chemotherapy hurts healthy cells along with abnormal cells. If chemotherapy works in controlling abnormal cells, then relatively normal blood cells will start to grow again. Low-dose chemotherapy agents include: cytarabine (Ara-C) and hydroxyurea (Hydrea). High-dose chemotherapy agents include: daunorubicin (Cerubidine), idarubicin (Idamycin), and mitoxanrone (Novantrone).

The part of the cell that contains our DNA or genetic code.

A medical condition that lasts a long time. A chronic illness can affect a person's lifestyle, ability to work, physical abilities and independence.

A person who gives advice, or counsel, to people who are coping with long-term illness. A chronic illness counselor helps people understand their abilities and limitations, cope with the stress, pain, and fatigue associated with long-term illness. A chronic illness counselor can often be located by contacting a local hospital.

A type of research that involves individual persons or a group of people. There are three types of clinical research. Patient-oriented research includes clinical trials which test how a drug, medical device, or treatment approach works in people. Epidemiology or behavioral studies look at the patterns and causes of disease in groups of people. Outcomes and health services research seeks to find the most effective treatments and health services.

A type of research study that tests how a drug, medical device, or treatment approach works in people. There are several types of clinical trials. Treatment trials test new treatment options. Diagnostic trials test new ways to diagnose a disease. Screening trials test the best way to detect a disease or health problem. Quality of life (supportive care) trials study ways to improve the comfort of people with chronic illness. Prevention trials look for better ways to prevent disease in people who have never had the disease.

Trials are in four phases: Phase I tests a new drug or treatment in a small group to see if it is safe. Phase II expands the study to a larger group of people to find out if it works. Phase III expands the study to an even larger group of people to compare it to the standard treatment for the disease; and Phase IV takes place after the drug or treatment has been licensed and marketed to find out the long-term impact of the new treatment.

To make copies. Bone marrow stem cells clone themselves all the time. The cloned stem cells eventually become mature blood cells that leave the bone marrow and enter the bloodstream.

To thicken. Normal blood platelets cause the blood to coagulate and stop bleeding.

A group of proteins that move freely in the bloodstream. These proteins support (complement) the work of white blood cells by fighting infections.

A medical approach that is not currently part of standard practice. Complementary medicine is used along with standard medicine. Alternative medicine is used in place of standard medicine. Example of CAM therapies are acupuncture, chiropractic, homeopathic, and herbal medicines. There is no complementary or alternative therapy that effectively treats bone marrow failure. Some CAM therapies may even hinder the effectiveness of standard medical care. Patients should talk with their doctor if they are currently using or considering using a complementary or alternative therapy.

A group of tests performed on a small amount of blood. The CBC measures the number of each blood cell type, the size of the red blood cells, the total amount of hemoglobin, and the fraction of the blood made up of red blood cells. Also called a CBC.

A procedure where umbillical cord stem cells are given to the patient through an intravenous (IV) line. Stem cells are collected from an umbilical cord right after the birth of a baby. They are kept frozen until needed. In time, donated stem cells given to the patient begin making new, healthy blood cells.

An imaging technique using x-ray technology and computerization to create a three-dimentional image of a body part. Also called a CT scan, it can be used to locate a blood clot in the body.

A response to treatment indicating that no sign of abnormal chromosomes are found. When a test is done on a patient with 5q deletion MDS, and there are no signs of an abnormal chromosome 5, then that patient has achieved a cytogenetic remission. Also called cytegenetic response.

(sie-toe-juh-NEH-tiks) The study of chromosomes (DNA), the part of the cell that contains genetic information. Some cytogenetic abnormalities are linked to different forms of myelodysplastic syndromes (MDS).

(sie-tuh-PEE-nee-uh) A shortage of one or more blood cell types. Also called a low blood count.

(sie-tuh-TOK-sik) A medicine that kills certain cells. Chemotherapy for MDS patients often involves the use of cytotoxic agents.

A test that helps doctors find out if a person has a problem with blood clotting.

(di-NO-vo) Brand new, referring to the first time something occurs. MDS that is untreated or that has no known cause is called de novo MDS.

The death of part of the intestine. This can happen if the blood supply in the intestine is cut off, for example, from a blood clot in the abdomen. Also called intestinal necrosis, ischemic bowel, dead gut.

A rare form of pure red cell aplasia that can be passed down from parent to child. Diamond-Blackfan anemia (DBA) is characterized by low red blood cell counts detected in the first year of life. Some people with DBA have physical abnormalities such as small head size, low frontal hairline, wide-set eyes, low-set ears. Genetic testing is used to diagnose DBA.

Vitamins, minerals, herbs and other substances meant to improve your nutritional intake. Dietary supplements are taken by mouth in the form of a pill, capsule, tablet or liquid.

To become distinct or specialized. In the bone marrow, young parent cells (stem cells) develop, or differentiate, into specific types of blood cells (red cells, white cells, platelets).

The gene that always expresses itself over a recessive gene. A person with a dominant gene for a disease has the symptoms of the disease. They can pass the disease on to children.

An inherited disease that may lead to bone marrow failure.

Refers to how well a graft (donor cells) is accepted by the host (the patient) after a bone marrow or stem cell transplant. Several factors contribute to better engraftment: physical condition of the patient, how severe the disease is, type of donor available, age of patient. Successful engraftment results in new bone marrow that produces healthy blood cells.

A type of white blood cell that kills parasites and plays a role in allergic reactions.

The study of patterns and causes of disease in groups of people. Epidemiology researchers study how many people have a disease, how many new cases are diagnosed each year, where patients are located, and environmental or other factors that influence disease.

(i-RITH-ruh-site) See red blood cell.

(i-rith-row-POY-uh-tun) A protein made by the kidneys. Erythropoietin, also called EPO, is created in response to low oxygen levels in the body (anemia). EPO causes the bone marrow to make more red blood cells. A shortage of EPO can also cause anemia.

A medicine used to help the bone marrow make more red blood cells. Epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) are erythropoietin-stimulating agents that can help boost the red blood cell count of some bone marrow failure patients. Also called red blood cell growth factor.

A form of estrogen, it is the most potent female hormone. It is also present in males. Estradiol is involved in many body functions beyond the reproductive system. Researchers are investigating the role of estradiol in the treatment of genetic bone marrow failure.

The cause or origin of a disease.

A criteria used for classifying different types of myelodysplastic syndromes (MDS). The FAB (French, American, British) Classification System was developed by a group of French, American and British scientists. This system is based on 2 main factors: the percentage of blast cells in bone marrow, and the percentage of blast cells in the bloodstream. The FAB system is somewhat outdated, but is still used by some doctors today. The World Health Organization (WHO) Classification System has largely replaced the FAB Classification System.

A rare inherited disorder that happens when the bone marrow does not make enough blood cells: red cells, white cells, and platelets. Fanconi anemia is diagnosed early in life. People with Fanconi anemia have a high likelihood of developing cancer. Genetic testing is used to diagnose Fanconi anemia.

(FER-i-tin) A protein inside of cells that stores iron for later use by your body. Sometimes ferritin is released into the blood. The ferritin level in the blood is called serum ferritin.

(FER-i-tin) A blood test used to monitor how much iron the body is storing for later use.

(fie-BRO-suss) Scarring of tissue. Fibrosis of the bone marrow is an feature seen in some types of unclassified myeldysplastic syndrome (MDS).

See fluorescence in situ hybridization.

(sy-TOM-uh-tree) A laboratory test that gives information about cells, such as size, shape, and percentage of live cells. Flow cytometry is the test doctors use to see if there are any proteins missing from the surface of blood cells. It is the standard test for confirming a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH).

(flor-EH-sense in SIT-tyoo hy-bru-duh-ZAY-shun) An important laboratory test used to help doctors look for chromosomal abnormalities and other genetic mutations. Fluorescence in situ hybridization, also called FISH, directs colored light under a microscope at parts of chromosomes or genes. Missing or rearranged chromosomes are identified using FISH.

(FOE-late) A B-vitamin that is found in fresh or lightly cooked green vegetables. It helps the bone marrow make normal blood cells. Most people get enough folate in their diet. Doctors may have people with paroxysmal nocturnal hemaglobinuria (PNH) take a man-made form of folate called folic acid.

See folate.

A laboratory test that looks at the whether red blood cells break apart too easily when they are placed in mild acid. This test has been used in the past to diagnose paroxysmal nocturnal hemoglobinuria (PNH). Most doctors now use flow cytometry, a more accurate method of testing for PNH. Ham Test is also called acid hemolysin test.

(hi-MA-tuh-crit) A blood test that measures the percentage of the blood made up of red blood cells. This measurement depends on the number of red blood cells and their size. Hematocrit is part of a complete blood count. Also called HCT, packed cell volume, PCV.

(hee-muh-TOL-uh-jist) A doctor who specializes in treating blood diseases and disorders of blood producing organs.

(hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow.

A condition that occurs when the body absorbs and stores too much iron. This leads to a condition called iron overload. In the United States, hemochromatosis is usually caused by a genetic disorder. Organ damage can occur if iron overload is not treated.

A protein in the red blood cells. Hemoglobin picks up oxygen in the lungs and brings it to cells in all parts of the body.

(hee-muh-gloe-buh-NYOOR-ee-uh) The presence of hemoglobin in the urine.

(hi-MOL-uh-suss) The destruction of red blood cells.

See human leukocyte antigen.

A part of the endocrine system that serves as the body's chemical messengers. Hormones move through the bloodstream to transfer information and instruction from one set of cells to another.

(LEW-kuh-site ANT-i-jun) One of a group of proteins found on the surface of white blood cells and other cells. These antigens differ from person to person. A human leukocyte antigen test is done before a stem cell transplant to closely match a donor and a recipient. Also called HLA.

A condition in which there are too many cells, for example, within the bone marrow. Patients with leukemia have hypercellular bone marrow filled with to many immature white blood cells.

A condition in which there are too few cells, for example, within the bone marrow. Patients with aplastic anemia have hypocellular bone marrow.

Usually refers to any condition with no known cause.

(i-myoo-no-KOM-pruh-mized) Occurs when the immune system is not functioning properly, leaving the patient open to infection. A person can be immunocompromised due to low white blood cell count or due to some medicines. Also called immune compromised.

(i-myoo-no-suh-PREH-siv) Drugs that lower the body's immune response and allow the bone marrow stem cells to grow and make new blood cells. ATG (antithymocyte globulin) or ALG (antilymphocyte globulin) with cyclosporine are used to treat bone marrow failure in aplastic anemia. Immunosuppressive drugs may help some patients with myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH).

A committee that makes sure a clinical trial is safe for patients in the study. Each medical center, hospital, or research facility doing clinical trials must have an active Institutional Review Board (IRB). Each IRB is made up of a diverse group of doctors, faculty, staff and students at a specific institution.

A system that turns patient data into a score. The score tells how quickly a myelodysplastic syndrome (MDS) case is progressing and helps predict what may happen with the patient's MDS in the future. Also called IPSS.

A method of getting fluids or medicines directly into the bloodstream over a period of time. Also called IV infusion.

A new drug, antibiotic drug, or biological drug that is used in a clinical trial. It also includes a biological product used in the laboratory for diagnostic purposes. Also called IND.

(kee-LAY-shun) A drug therapy to remove extra iron from the body. Patients with high blood iron (ferritin) levels may receive iron chelation therapy. The U.S. Food and Drug Administratin (FDA) has approved two iron chelators to treat iron overload in the U.S.: deferasirox, an oral iron chelator, and deferoxamine, a liquid given by injection.

A condition that occurs when too much iron accumulates in the body. Bone marrow failure disease patients who need regular red blood cell transfusions are at risk for iron overload. Organ damage can occur if iron overload is not treated.

(iss-KEE-mee-uh) Occurs when the blood supply to specific organ or part of the body is cut off, causing a localized lack of oxygen.

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Glossary of Terms | Aplastic Anemia and MDS International ...

Skin Stem Cells Comments Off on Glossary of Terms | Aplastic Anemia and MDS International … | November 22nd, 2017

Our initial application established the goals of our project and the reasons for our study. Arthritis is the result of degeneration of cartilage (the tissue lining the joints) and leads to pain and limitation of function. Arthritis and other rheumatic diseases are among the most common of all health conditions and are the number one cause of disability in the United States. The annual economic impact of arthritis in the U.S. is estimated at over $120 billion, representing more than 2% of the gross domestic product. The prevalence of arthritic conditions is also expected to increase as the population increases and ages in the coming decades. Current treatment options for osteoarthritis are limited to pain reduction and joint replacement surgery. Stem cells have tremendous potential for treating disease and replacing or regenerating the diseased tissue. In this project our objective is to use cells derived from stems cells to treat arthritis. We have completed our experiments as per our proposed timeline and have met milestones outlined in our grant submission. We have established conditions for converting stem cells into cartilage tissue cells that can repair bone and cartilage defects in laboratory models. We have identified several cell lines with the highest potential for tissue repair. We optimized culture conditions to generate the highest quality of tissue. In our initial experiments we found no evidence of cell rejection response in vivo. We have testing efficacy of the most promising cell lines in regenerating healthy repair tissue in cartilage defects and have selected a preclinical candidate.The next step is to plan safety and efficacy studies for the preclinical phase, identify collaborators with the facilities to obtain, process, and provide cell-based therapies, and identify clinical collaborators in anticipation of clinical trials. If necessary we will also identify commercialization partners. We also anticipate that stem cells implanted in arthritic cartilage will treat the arthritis in addition to producing tissue to heal the defect in the cartilage. An approach that heals cartilage defects as well as treats the underlying arthritis would be very valuable. If our research is successful, this could lead to first treatment of osteoarthritis that alters the progression of the disease. This treatment would have a huge impact on the large numbers of patients who suffer from arthritis as well as in reducing the significant economic burden created by arthritis.

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Stem Cell-Based Therapy for Cartilage Regeneration and ...

IPS Cell Therapy Comments Off on Stem Cell-Based Therapy for Cartilage Regeneration and … | November 22nd, 2017

Scientists reported Wednesday that they genetically modified stem cells to grow skin that they successfully grafted over nearly all of a child's body - a remarkable achievement that could revolutionize treatment of burn victims and people with skin diseases.

The research, published in the journal Nature, involved a 7-year-old boy who suffers from a genetic disease known as junctional epidermolysis bullosa (JEB) that makes skin so fragile that minor friction such as rubbing causes the skin to blister or come apart.

By the time the boy arrived at Children's Hospital of Ruhr-University in Germany in 2015, he was gravely ill. Doctors noted that he had "complete epidural loss" on about 60 percent of his body surface area, was in so much pain that he was on morphine, and fighting off a systemic staph infection. The doctors tried everything they could think of: Antibiotics, changing dressings, grafting skin donated by his father. But nothing worked, and they told his parents to prepare for the worst.

"We had a lot of problems in the first days keeping this kid alive," Tobias Hirsch, one of the treating physicians, recalled in a conference call with reporters this week.

Hirsch and his colleague Tobias Rothoeft began to scour the medical literature for anything that might help and came across an article describing a highly experimental procedure to genetically engineer skin cells. They contacted the author, Michele De Luca, of the Center for Regenerative Medicine University of Modena and Reggio Emilia in Italy. De Luca flew out right away.

Using a technique he had used only twice before and even then only on small parts of the body, De Luca harvested cells from a four-square-centimeter patch of skin on an unaffected part of the boy's body and brought them into the lab. There, he genetically modified them so that they no longer contained the mutated form of a gene known to cause the disease and grew the cells into patches of genetically modified epidermis. They discovered, the researchers reported, that "the human epidermis is sustained by a limited number of long-lived stem cells which are able to extensively self-renew."

In three surgeries, the child's doctors took that lab-grown skin and used it to cover nearly 80 percent of the boy's body - mostly on the limbs and on his back, which had suffered the most damage. The procedure was permitted under a "compassionate use" exception that allows researchers under certain dire circumstances to make a treatment available even though it is not approved by regulators for general use. Then, over the course of the next eight months while the child was in the intensive care unit, they watched and waited.

The boy's recovery was stunning.

The regenerated epidermis "firmly adhered to the underlying dermis," the researchers reported. Hair follicles grew out of some areas. And even bumps and bruises healed normally. Unlike traditional skin grafts that require ointment once or twice a day to remain functional, the boy's new skin was fine with the normal amount of washing and moisturizing.

"The epidermis looks basically normal. There is no big difference," De Luca said. He said he expects the skin to last "basically the life of the patient."

In an analysis accompanying the main article in Nature, Mariacelest Aragona and Cedric Blanpain wrote that this therapy appears to be one of the few examples of truly effective stem-cell therapies. The study "demonstrates the feasibility and safety of replacing the entire epidermis using combined stem-cell and gene therapy," and also provides important insights into how different types of cells work together to help our skin renews itself.

They said there are still many other lingering questions, including whether such procedures might work better in children than adults and whether there would be longer-term adverse consequences, such as the development of cancer.

There are also many challenges to translating this research to treating wounds sustained in fires or other violent ways. In the skin disease that was treated in the boy, the epidermis is damaged but the layer beneath it, the dermis, is intact. The dermis is what the researchers called an ideal receiving bed for the lab-grown skin. But if deeper layers of the skin are burned or torn off, it's possible that the artificial skin would not adhere as well.

"No matter how you prepare, it's a bad situation," De Luca said. For the time being, he says he's continuing to study the procedure in two clinical trials that involve genetic diseases.

Meanwhile, Hirsch and Rothoeft report that the boy is continuing to do well and is not on any medication for the first time in many years. Doctors are carefully monitoring the child for any signs that there may be some cells that were not corrected and that the disease may re-emerge, but right now that does not appear to be happening in the transplanted areas. However, the child does have some blistering in about 2 to 3 percent of his body in non-grafted areas and they are considering whether to replace that skin as well.

But for now, they are giving the boy time to be a boy, Rothoeft said: "The kid is now back to school and plays soccer and spends other days with the children."

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Genetically modified skin grown from stem cells saved a 7 ...

Skin Stem Cells Comments Off on Genetically modified skin grown from stem cells saved a 7 … | November 14th, 2017

T

he complications of the little boys genetic skin disease grew as he did. Tiny blisters had covered his back as a newborn. Then came the chronic skin wounds that extended from his buttocks down to his legs.

By June 2015, at age 7, the boy had lost nearly two-thirds of his skin due to an infection related to the genetic disorder junctional epidermolysis bullosa, which causes the skin to become extremely fragile. Theres no cure for the disease, and it is often fatal for kids. At the burn unit at Childrens Hospital in Bochum, Germany, doctors offered him constant morphine and bandaged much of his body, but nothing not even his fathers offer to donate his skin worked to heal his wounds.

We were absolutely sure we could do nothing for this kid, Dr. Tobias Rothoeft, a pediatrician with Childrens Hospital in Bochum, which is affiliated with Ruhr University. [We thought] that he would die.

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As a last-ditch effort, the boys father asked if there were any available experimental treatments. The German doctors reached out to Dr. Michele De Luca, an Italian stem cell expert who heads the Center for Regenerative Medicine at the University of Modena and Reggio Emilia, to see if a transplant of genetically modified skin cells might be possible. De Luca knew the odds were against them such a transplant had only been performed twice in the past, and never on such a large portion of the body. But he said yes.

The doctors were ultimately able to reconstruct fully functional skin for 80 percent of the boys body by grafting on genetically modified cells taken from the boys healthy skin. The researchers say the results of this single-person clinical trial, published on Wednesday in Nature, show that transgenic stem cells can regenerate an entire tissue. De Luca told reporters the procedure not only offers hope to the 500,000 epidermolysis bullosa patients worldwide but also could offer a blueprint for using genetically modified stem cells to treat a variety of other diseases.

To cultivate replacement skin, the medical team took a biopsy the size of a matchbook from the boys healthy skin and sent it to De Lucas team in Italy. There, researchers cloned the skin cells and genetically modified them to have a healthy version of the gene LAMB3, responsible for making the protein laminin-332. They grew the corrected cultures into sheets, which they sent back to Germany. Then, over a series of three operations between October 2015 and January 2016, the surgical team attached the sheets on different parts of the boys body.

The gene-repaired skin took, and spread. Within just a month the wounds were islands within intact skin. The boy was sent home from the hospital in February 2016, and over the next 21 months, researchers said his skin healed normally. Unlike burn patients whose skin grafts arent created from genetically modified cells the boy wont need ointment for his skin and can regrow his hair.

And unlike simple grafts of skin from one body part to another, we had the opportunity to reproduce as much as those cells as we want, said plastic surgeon Dr. Tobias Hirsch, one of the studys authors. You can have double the whole body surface or even more. Thats a fantastic option for a surgeon to treat this child.

Dr. John Wagner, the director of the University of Minnesota Masonic Childrens Hospitals blood and marrow transplant program, told STAT the findings have extraordinary potential because, until now, the only stem cell transplants proven to work in humans was of hematopoietic stem cells those in blood and bone marrow.

Theyve proven that a stem cell is engraftable, Wagner said. In humans, what we have to demonstrate is that a parent cell is able to reproduce or self-renew, and differentiate into certain cell populations for that particular organ. This is the first indication that theres another stem cell population [beyond hematopoietic stem cells] thats able to do that.

The researchers said the aggressive treatment outlined in the study necessary in the case of the 7-year-old patient could eventually help other patients in less critical condition. One possibility, they noted in the paper, was to bank skin samples from infants with JEB before they develop symptoms. These could then be used to treat skin lesions as they develop rather than after they become life-threatening.

The treatment might be more effective in children, whose stem cells have higher renewal potential and who have less total skin to replace, than in adults, Mariaceleste Aragona and Cdric Blanpain, stem cell researchers with the Free University of Brussels, wrote in an accompanying commentary for Nature.

But De Luca said more research must be conducted to see if the methods could be applied beyond this specific genetic disease. His group is currently running a pair of clinical trials in Austria using genetically modified skin stem cells to treat another 12 patients with two different kinds of epidermolysis bullosa, including JEB.

For the 7-year-old boy, life has become more normal now that it ever was before, the researchers said. Hes off pain meds. While he has some small blisters in areas that didnt receive a transplant, they havent stopped him from going to school, playing soccer, or behaving like a healthy child.

The kid is doing quite well. If he gets bruises like small kids [do], they just heal as normal skin heals, Rothoeft said. Hes quite healthy.

Southern Correspondent

Max covers hospitals and health care.

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'Extraordinary' tale: Stem cells heal a young boy's lethal ...

Skin Stem Cells Comments Off on ‘Extraordinary’ tale: Stem cells heal a young boy’s lethal … | November 14th, 2017

A new therapy could restore healthy and protective skin to patients with a rare genetic disease.

iStock.com/Andrey Prokhorov

By Kelly ServickNov. 8, 2017 , 1:00 PM

A 7-year-old who lost most of his skin to a rare genetic disease has made a dramatic recovery after receiving an experimental gene therapy, researchers announced today. The treatmenta whole-body graft of genetically modified stem cellsis the most ambitious attempt yet to treat a severe form of epidermolysis bullosa (EB), an often-fatal group of conditions that cause skin to blister and tear off at the slightest touch.

The new approach can address only a subset of the genetic mutations that cause EB. But the boys impressive recoveryhes now back inschool and is even playing soccercould yield insights that help researchers use stem cells to treat other genetic skin conditions.

It is very unusual that we would see a publication with a single case study anymore, but this one is a little different, says Jakub Tolar, a bone marrow transplant physician at the Masonic Cancer Center, University of Minnesotain Minneapolis who is developing therapies for EB. This is one of these [studies] that can determine where the future of the field is going to go.

EB results from mutations to any of several genes that encode proteins crucial for anchoring the outer layer of skin, the epidermis, to the tissue below. The missing or defective protein can cause skin to slough off from minor damage, creating chronic injuries prone to infection. Some forms of EB can be lethal in infancy, and some predispose patients to an aggressive and deadly skin cancer. The only treatment involves painfully dressing and redressing wounds daily. Bandage costs can approach $100,000 a year, says Peter Marinkovich, a dermatologist at Stanford University in Palo Alto, California, who treats EB patients. Theyre like walking burn victims, he says.

In fact, the new approach is similar to an established treatment for severe burns, in which sheets of healthy skin are grown from a patients own cells and grafted over wounds. But stem cell biologist and physician Michele De Luca of the University of Modena and Reggio Emilia in Italy and his colleagues have been developing a way to counteract an EB-causing mutation by inserting a new gene into the cells used for grafts. His group has already treated two EB patients with this approach. They publishedencouraging resultsfrom their first attemptwith small patches of gene-corrected skin on a patients legsin 2006.

In 2015, De Lucas team got a desperate request from doctors in Germany. Their young patient had a severe form of the disease known as junctional EB, caused by a mutation in a gene encoding part of the protein laminin 332, which makes up a thin membrane just below the epidermis. It was the same gene De Lucas team was targeting in an ongoing clinical trial, but this case was especially dire: Lacking most of his skin, the boy had contracted multiple infections and was in a life-threatening septic state. The emergency treatment would be the first test of their gene therapy approach over such a large and severely damaged area.

De Lucas team used a patch of skin a little bigger than a U.S. postage stamp from an unblistered part of the boys groin to culture epidermal cells, which include stem cells that periodically regenerate the skin. They infected those cells with a retrovirus bearing healthy copies of the needed gene,LAMB3, and grew them into sheets ranging from 50 to 150 square centimeters. In two surgeries, a team at Ruhr University in Bochum, Germany, covered the boys arms, legs, back, and some of his chest in the new skin.

After a month,most of the new skin had begun to regenerate, covering 80% of the boys body in strong and elastic epidermis, the researchers report online today inNature. Whats more, hes developed no blisters in the grafted areas in the 2 years since the surgery.

Other researchers have long been concerned that using a retrovirus to insert genes at random points in cells genomes might cause cancer. (In the early 2000s, five children who participated in a retrovirus-based gene therapy trial for severe combined immunodeficiencydeveloped leukemia.) But the current study found no evidence that the insertion affected cancer genes.

De Luca and colleagues were also able to track which grafted cells regenerated the skin over time by using the different locations of the genetic insert as markers for individual cells and their progeny. They found that most cells from the graft disappeared after a few months, but a small population of long-lived cells called holoclones formed colonies that renewed the epidermis.

Epidermal stem cells known as holoclones (shown in pink) were responsible for regenerating the young epidermolysis bullosapatients skin, whileother cell types disappeared over time.

News & Views/Nature; adapted by E. Petersen/Science

Thats an important lesson, Tolar says; it suggests that future attempts to correct genetic skin diseases should focus on culture conditions that nourish these stem cells, and potentially even target them for modification. If you have a gene correction strategy, he says, youd better have these primitive epidermal stem cells in mind.

The current results could benefit several thousand EB patients across the world, Marinkovich says, but it wont work for all of them. More than half have a form of the disease called EB simplex, which is causednot by a missing protein, but by mutations that produce an active but dysfunctional protein. For these errors, correction with a gene-editing tool like CRISPR makes more sense, De Luca says.

The grafts also cant repair damage to internal surfaces such as the esophagus, Tolar notes, which occurs in some EB cases. Fortunately, that wasnt an issue for the boy in this study. The treatment is a good step in the right direction, he says, but its not curative.

Both De Luca and Marinkovichs teams are exploring a similar gene therapy for another major form of the disease, called dystrophic EB, caused by a different genetic error affecting a larger protein. Biotech companies are working with each group to test the approach in larger clinical trials.

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A boy with a rare disease gets new skin, thanks to gene ...

Skin Stem Cells Comments Off on A boy with a rare disease gets new skin, thanks to gene … | November 14th, 2017

In a breakthrough treatment, researchers at a burn unit in Europe found a way to replace 80 percent of a boys skin using a combination of gene therapy and stem cells. The grafted skin attached to his body has continued to replace itself, even months later.

The patient - a boy who was 7 years old at the time of the treatment - was born with a rare skin condition called junctional epidermolysis bullosa. The condition causes the outer layer of the skin to peel away easily from the lower skin layers, making it incredibly fragile and prone to injury.

This is a very severe, devastating disease, where kids suffer a lot, said Dr. Michele De Luca, one of the authors of the research.

Experts not involved in the research have said this successful grafting treatment is a big step for those suffering from genetic skin conditions like this one.

This is really quite exciting, to have this translation for these patients, said Dr. Dennis Orgill, medical director of the Brigham and Womens Hospital Wound Center in Boston, who was not involved with the study. "That they can do these genetic manipulations and then have a long term result, which theyve demonstrated here, is a major breakthrough."

In this case, the treatment may have been lifesaving. The patient arrived at the hospital with a life-threatening bacterial skin infection spread over much of his body. Over the following weeks, his doctors tried everything they could to treat him without success.

Out of options, his treatment team was preparing to start end-of-life care when his parents pleaded with them to try an experimental therapy.

Surgeons in Germany took a sample of the boys skin, less than one square inch in size, that was unharmed by the bacterial infection. In a lab, researchers infected the skin biopsy with a virus specially designed to alter the genetic code within the skin cells, correcting the mutation responsible for his fragile skin. The researchers "grew" the skin and used it to surgically replace the patients blistered and destroyed skin.

After 21 months, the new skin is regenerating itself without problems and has been resilient; it can hold up to normal wear much better than his original skin.

While this result only applies to one rare skin disorder right now, experts said the approach could be used more widely for other diseases in the future.

We are running other clinical trials on other kinds of junctional epidermolysis bullosa," De Luca said. "In the future, it could be applied to other genetic diseases of the skin.

Researchers hope that it could help other people with seriously damaged skin in the future, too.

This technology could be extended into other patients with genetic conditions, or patients with extensive burns, Orgill said.

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Doctors replace boys skin using breakthrough gene therapy ...

Skin Stem Cells Comments Off on Doctors replace boys skin using breakthrough gene therapy … | November 14th, 2017

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(CNN) - For the first time, doctors were able to treat a child who had a life-threatening rare genetic skin disease through a transplant of skin grown using genetically modified stem cells.

The grafts replaced 80% of the boy's skin.

The skin of his arms, legs, back and flanks, and some of the skin on his stomach, neck and face was missing or severely affected due to epidermolysis bullosa.

The compassionate-use experimental treatment is detailed in a case study published in the journal Nature on Wednesday.

Skin as fragile as a butterfly's wings -- that's how children with epidermolysis bullosa are described and why they're often called butterfly children.

The disease, of which there are five major types and at least 31 subtypes, is incurable. People with the condition have a defect in the protein-forming genes necessary for skin regeneration.

About 500,000 people worldwide are affected by forms of the disease. More than 40% of patients die before reaching adolescence.

Their skin can blister and erode due to something as simple as bumping into something or even the light friction of clothing, according to an email from Dr. Jouni Uitto, a professor and chairman of the Department of Dermatology and Cutaneous Biology at the Sidney Kimmel Medical College in Philadelphia. Uitto was not involved with this study.

Epidermolysis bullosa makes the skin incredibly susceptible to infections, and in the case of 7-year-old Hassan, whose treatment was detailed in Nature, those infections can be life-threatening.

A week after he was born in Syria, Hassan had a blister on his back, his father said through an interpreter in an interview provided by the hospital in Germany where the boy was treated.

Hassan's last name, as well as the first names of his family members, are not being disclosed to protect the privacy of the family.

In his first few weeks of life, Hassan was immediately diagnosed with epidermolysis bullosa, and their doctor in Syria told Hassan's family that there was no cure or therapy.

Over the years, their efforts to find help for their son's disease led the family to the Muenster University hospital in Germany in 2015, when Hassan was 7. His condition worsened, and he struggled with severe sepsis and a high fever. He weighed just over 37 pounds.

They didn't think he would make it, and doctors at Muenster decided in summer 2015 to transfer Hassan to the Ruhr-Universitt Bochum's University Hospitals, including the burn center -- one of the oldest in the country.

By the time Hassan arrived at Bochum, he had lost two-thirds of his surface skin.

"We had a lot of problems in first days just keeping him alive," said Dr. Tobias Rothoeft, consultant at the University Children's Hospital at Katholisches Klinikum Bochum.

Doctors tried to promote healing by changing his dressings and treating him with antibiotics, as well as putting him on an aggressive nutrition schedule, but nothing helped. They even tried transplanting skin from Hassan's father.

"By that time, he had lost 60% of his epidermis, the upper skin layer, and had 60% open wounds all over his body," said Dr. Maximilian Kueckelhaus of the Department of Plastic Surgery at Bochum's Burn Center.

Every approach failed, so the doctors prepared Hassan's family for what end-of-life care would entail. But the parents pleaded, asking the doctors to consult studies and research for experimental treatments that might help.

They found Dr. Michele De Luca at the University of Modena's Center for Regenerative Medicine in Italy. His publications described an experimental treatment transplanting genetically modified epidermal stem cells that healed small, non-life-threatening wounds in adults.

The medical team reached out to De Luca, asking whether he could help them replicate the procedure on a larger scale to help Hassan, and he agreed. De Luca told Hassan's parents that he believed there was a 50% chance of the treatment being successful.

They were more than willing to accept the risk, to do anything to help their son have a chance at a normal life.

Hassan "was in severe pain and was asking a lot of questions: 'Why do I suffer from this disease? Why do I have to live this life? All children can run around and play. Why am I not allowed to play soccer?' I couldn't answer these questions," his father said. "It was a tough decision for us, but we wanted to try for Hassan."

To obtain the skin's stem cells, the doctors took a small biopsy -- only accounting for 1 square inches -- from an unaffected part of Hassan's skin. The stem cells were processed by De Luca in Italy. A healthy version of the gene that is normally defective in epidermolysis bullosa patients was added to the cells, along with retroviral vectors: virus particles that assist the gene transfer.

This genetic transfer would essentially "correct" the cells.

The single cells were grown and cultivated on plastic and fibrin substrate, which is used to treat large skin burns, to form a large piece of epidermis. This method enabled the researchers to grow as much skin as they needed. The whole process took three to four weeks, Kueckelhaus said.

Once the sheets were ready, they were transferred from Italy to Germany and transplanted onto the well-cleaned wounds right away during two surgeries. The first procedure in October 2015 applied the sheets to Hassan's arms and legs. The second surgery, in November, grafted the sheets to Hassan's entire back and the other affected areas.

Hassan began to improve immediately. The researchers noticed that the grafts were not rejected; they bound to all of the areas they were transplanted.

"For everyone that was involved, taking off the bandages and seeing for the first time that this is working out, that the transplants are actually attached to the patient and growing skin, that's an incredible moment," Kueckelhaus said.

Hassan was discharged from the hospital in February 2016.

After steady followups over 21 months, the researchers found that Hassan's new skin healed normally, didn't blister anymore, and was resistant to stress. It was even growing hair. Unlike some skin graft patients, he doesn't require any ointment to keep his skin smooth and hydrated. And like any growing kid, he bruises and recovers normally.

They also learned that only a few stem cells contribute to the long-term maintenance of the epidermis, shedding light on cellular hierarchy in this regard.

"The investigators removed of small piece of patient's skin, isolated cells with stem cell potential for growth, introduced a normal copy of the mutated gene to the cells, propagated a large number of these cells in culture and then grafted them back to the skin," Uitto said. "This concept is not new, but what is remarkable here is that they were able to change essentially the entire skin of the patient with normal cells."

Hassan's family is currently living in Germany. Hassan, now 9, is able to go to school and play sports, but he maintains a schedule of frequent monitoring at the hospital to ensure that the initial success of the treatment continues. The area of his skin that was not treated sometimes shows small blisters, and if it worsens, he may receive transplants there as well.

"Seeing him 18 months after the initial surgery with an intact skin is incredible because he has been in the ICU for so long," Kueckelhaus said. "He had bandages all over his body except his hands, feet and face. He was on extremely strong pain medication. So the quality of life was really, really bad for him. Seeing him play soccer, play sports, play with other kids, that is just amazing because that's something he couldn't do before."

"It felt like a dream for us," the boy's father said. "Hassan feels like a normal person now. He plays. He's being active. He loves life."

Everything points to a good long-term outcome for Hassan.

The researchers will continue to monitor him for complications. Sometimes, genetic modifications can cause malignancies in cells.

"That is of course one thing we really have to be aware of," Kueckelhaus said. "However, analyzing the integration profile of that gene into the boy's DNA, which we did, we saw that it's mostly in areas that don't cause too much concern about developing malignancies."

Epidermolysis bullosa patients can be at a very high risk of developing skin cancer simply because of the disease. Because Hassan now has intact skin and intact DNA, this risk might even decrease, but that will have to be proved through follow-up, Kueckelhaus said.

Given that this was one successful outcome for one patient, the experimental treatment can't be applied for other patients just yet. De Luca is conducting clinical trials using the treatment.

"This is one case with a distinct type of EB, and further studies will show whether this approach is applicable to other forms of EB as well," Uitto said. "It should be noted that in some severe forms of EB, the patients also suffer from fragility of the gastrointestinal and vesico-urinary tract, and some forms are associated with the development of muscular dystrophy. Obviously, gene therapy of the skin cannot correct them, and these issues have to be addressed in further studies."

Hassan's treatment also cost hundreds of thousands of dollars. Although the process could be optimized, doctors would still have to individually grow transplants for each patient, which could get very expensive.

But for patients' families, epidermolysis bullosa is already expensive.

"Standard maintenance treatment of patients with EB, including daily bandaging, antibiotics and special moisturizer, as well as frequent hospitalizations, can be extremely costly, and gene correction as described in this paper may well be cost-effective over the lifetime of these patients," Uitto noted.

Brett Kopelan, executive director of the Dystrophic Epidermolysis Bullosa Research Association of America, has a 10-year-old daughter, Rafi, with recessive dystrophic EB. Between January and August, $751,1778 for wound/burn dressings was charged to Kopelan's insurance company, he says. That doesn't account for drugs or hospital visits and surgeries.

Kopelan's nonprofit sends free supplies and bandages to families. The nonprofit can provide its employees with insurance that covers the medical equipment, but that isn't the case for everyone impacted by the condition, he said.

Kopelan is hopeful about the results of the study. The baths and bandage changes that are necessary for epidermolysis bullosa patients to stave off life-threatening infections can last hours and feel torturous.

"Do you remember the last time you got a paper cut and put Purell on it? It burned, right? Now think of 60% of body being an open wound, and opioids don't really work for this kind of pain," Kopelan wrote in an email. "This is what make EB kids and adults the strongest people on Earth."

The study "confirms our hopes that gene therapy is potentially the most efficacious path forward to providing a significant treatment option for those with epidermolysis bullosa," Kopelan said. "While it's important to remember that this is only one patient and more work needs to be done to demonstrate how effective this gene therapy platform may prove to be, I am very enthused."

"I wish that all children with the same disease could be treated in this way," Hassan's father said.

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Scientists replace skin using genetically modified stem cells

Skin Stem Cells Comments Off on Scientists replace skin using genetically modified stem cells | November 14th, 2017