27 Oktober, 2010

Stem cell transplant

Definition

A stem cell transplant is the infusion of healthy stem cells into your body. A stem cell transplant may be necessary if your bone marrow stops working and doesn't produce enough healthy stem cells. A stem cell transplant can help your body make enough healthy white blood cells, red blood cells or platelets, and reduce your risk of life-threatening infections, anemia and bleeding.

Although the procedure to replenish your body's supply of healthy blood-forming cells is generally called a stem cell transplant, it's also known as a bone marrow transplant or an umbilical cord blood transplant, depending on the source of the stem cells. Stem cell transplants can use cells from your own body (autologous stem cell transplant), or they can use stem cells from donors (allogenic stem cell transplant).

Why it's done

Stem cell transplants are used to treat people whose stem cells have been damaged by disease or the treatment of a disease. Stem cell transplants can benefit people with a variety of both cancerous (malignant) and noncancerous (nonmalignant) diseases.

A stem cell transplant may help your body:

  • Replace dysfunctional bone marrow. For instance, in aplastic anemia, a noncancerous condition, your bone marrow doesn't make enough new blood cells. A stem cell transplant procedure first destroys the dysfunctional marrow with powerful drugs or radiation, and then healthy stem cells are infused. If all goes well, the new stem cells migrate to the marrow and begin working normally.
  • Destroy unhealthy bone marrow that may contain cancer cells. In the case of cancer, such as leukemia, a stem cell transplant procedure may first help rid the bone marrow of cancer cells. When healthy stem cells are then transplanted, normal cell production can resume. In addition, immune factors in the transplanted cells may help destroy any cancer cells that remain in your bone marrow.

Risks

A stem cell transplant poses many risks of complications, some potentially fatal. Although some people experience few problems with a transplant, others must endure frequent tests and repeated hospitalizations.

Complications that can arise with a stem cell transplant include:

  • Graft-versus-host disease
  • Stem cell (graft) failure
  • Organ damage
  • Cataracts
  • Secondary cancers
  • Death

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

Graft-versus-host disease: A potential risk when stem cells come from donors
If you're undergoing a transplant that will use stem cells from a donor (allogenic stem cell transplant), you may be at risk of graft-versus-host disease. This condition occurs when a donor's transplanted stem cells attack your body. Graft-versus-host disease can be mild or severe. It can occur soon after your transplant or months to years later.

Graft-versus-host disease can cause skin rashes, abdominal pain, diarrhea, nausea and vomiting. Over time it can cause other complications and chronic illnesses. Your doctor will monitor you closely for signs and symptoms of graft-versus-host disease.

What they are and what they do

Researchers believe stem cells offer great promise for new medical treatments. Learn about stem cell types, current and possible uses, ethical issues and the state of research.

You've heard about stem cells in the news, and perhaps you've wondered if they might help you or a loved one with a serious disease. You may wonder what stem cells are, how they're being used to treat disease and injury, and why they're the subject of such vigorous debate.

Here are some answers to frequently asked questions about stem cells.

Why is there such an interest in stem cells?

Researchers hope stem cell studies can help to:

  • Increase understanding of how diseases occur. By watching stem cells mature into cells that eventually become bones, heart muscle, nerve cells, and other organs and tissue, researchers and doctors may better understand how a variety of diseases and conditions develop.
  • Generate healthy cells to replace diseased cells (regenerative medicine). Researchers hope they can train stem cells into becoming specific cells so that those specialized cells can be used to regenerate and repair diseased or damaged tissues in people. People who might benefit from stem cell therapies include those with spinal cord injuries, type 1 diabetes, Parkinson's disease, Alzheimer's disease, heart disease, stroke, rheumatoid arthritis, osteoarthritis and multiple sclerosis. Stem cells could also be grown to become new tissue for use in transplant medicine.
  • Test new drugs for safety and effectiveness. Before using new drugs in people, researchers could use stem cells to test the safety and quality of investigational drugs. For instance, nerve cells could be generated in order to test a new drug for a nerve disease. Tests could show whether the new drug had any effect on the cells and whether the cells were harmed.

What are stem cells?

Stem cells: The body's master cells

Stem cells are the body's master cells. All other cells arise from stem cells, including blood cells, nerve cells and others.

Stem cells are the body's raw materials — cells from which all other cells with specialized functions are generated. Under the right conditions in the body or a laboratory, stem cells divide to form more cells, called daughter cells. These daughter cells either become new stem cells (self-renewal) or become specialized cells (differentiation) with a more specific function, such as blood cells, brain cells, heart muscle or bone. Stem cells are unique — no other cell in the body has the natural ability to generate new cell types.

Where do stem cells come from?

Researchers have discovered several sources of stem cells:

  • Embryonic stem cells. These stem cells come from embryos that are four to five days old. At this stage, an embryo is called a blastocyst and has about 150 cells. These are pluripotent (ploo-RIP-uh-tunt) stem cells, meaning they can divide into more stem cells or they can specialize and become any type of body cell. Because of this versatility, embryonic stem cells have the highest potential for use to regenerate or repair diseased tissue and organs in people.
  • Adult stem cells. These stem cells are found in small numbers in most adult tissues, such as bone marrow. Adult stem cells are also found in children and in placentas and umbilical cords. Because of that, a more precise term is somatic stem cell, meaning "of the body." Until recently, it was believed that adult stem cells could only create similar types of cells. For instance, it was thought that stem cells residing in the bone marrow could give rise only to blood cells. However, emerging evidence suggests that adult stem cells may be more versatile than previously thought and able to create unrelated types of cells after all. For instance, bone marrow stem cells may be able to create muscle cells. This research has led to early-stage clinical trials to test usefulness and safety in people.
  • Adult cells altered to have properties of embryonic stem cells (induced pluripotent stem cells). Scientists have successfully transformed regular adult cells into stem cells using a technique called nuclear reprogramming. By altering the genes in the adult cells, researchers can reprogram the cells to act similarly to embryonic stem cells. This new technique may help researchers avoid the controversies that come with embryonic stem cells, and prevent immune system rejection of the new stem cells. But, it's not yet known if altering adult cells will cause adverse effects in humans. Researchers have been able to take regular connective tissue cells and reprogram them to become heart cells. The new heart cells were injected into mice with heart failure, where they improved heart function and survival time.
  • Amniotic fluid stem cells. Researchers have also discovered stem cells in amniotic fluid. Amniotic fluid fills the sac that surrounds and protects a developing fetus in the uterus. Researchers have identified stem cells in samples of amniotic fluid drawn from pregnant women during a procedure called amniocentesis. During this test, a doctor inserts a long, thin needle into a pregnant woman's abdomen to collect amniotic fluid. The fluid can be tested for abnormalities, such as Down syndrome, and fetal maturity. The procedure is generally considered safe for the developing fetus and the mother. More study of amniotic fluid stem cells is needed to understand their potential.

Why is there a controversy about using embryonic stem cells?

Embryonic stem cells are obtained from early-stage embryos — a group of cells that forms when a woman's egg is fertilized with a man's sperm. Extracting stem cells from embryos raises significant ethical questions.

Where do these embryos come from?

The embryos being used in embryonic stem cell research come from eggs that were fertilized at in vitro fertilization clinics but never implanted in a woman's uterus because they were no longer wanted or needed. The excess embryos were frozen and later voluntarily donated for research purposes. The stem cells can live and grow in special solutions in test tubes or petri dishes in laboratories.

Why can't researchers use adult stem cells instead?

While research into adult stem cells is promising and moving forward rapidly, adult stem cells may not be as versatile and durable as embryonic stem cells are. Adult stem cells may not be able to be manipulated to produce all cell types, which limits how they can be used to treat diseases, and they don't seem to have the same ability to multiply that embryonic stem cells do. They're also more likely to contain abnormalities due to environmental hazards, such as toxins, or from errors acquired by the cells during replication. However, researchers have found that adult stem cells are more adaptable than was initially suspected. There have been significant advances in work with adult stem cells, and more studies are under way.

What are stem cell lines and why do researchers want to use them?

A stem cell line is a group of cells that all descend from a single original stem cell. Cells in a stem cell line keep growing but don't differentiate into specialized cells. Ideally, they remain free of genetic defects and continue to create more stem cells. Clusters of cells can be taken from a stem cell line and frozen for storage or shared with other researchers. That way, researchers don't have to get stem cells from an embryo itself.

What is stem cell therapy (regenerative medicine) and how does it work?

Stem cell therapy, also known as regenerative medicine, is the replacement of diseased, dysfunctional or injured cells with stem cells or their derivatives. It's somewhat similar to the organ transplant process but uses cells instead of organs.

Researchers grow stem cells in the lab. These stem cells are manipulated to make them specialize into specific types of cells, such as heart muscle cells, blood cells or nerve cells. This manipulation may involve changing the material in which the stem cells are grown or even injecting genes into the cells. The specialized cells could then be implanted into a person. For example, if the person had heart disease, the cells could be injected into the heart muscle. The healthy, transplanted heart cells could then contribute to repairing defective heart muscle. In fact, researchers have already shown that adult bone marrow cells guided to become heart-like cells can repair heart tissue in mice, and much more research is ongoing.

Have stem cells already been used to treat diseases?

Yes, stem cell transplants, also known as bone marrow transplants, have been performed in the United States since the late 1960s. These transplants use adult stem cells.

Adult stem cells are being tested in other applications, including a number of degenerative diseases, such as heart failure. Stem cells from umbilical cord blood have been successfully used in clinical trials to treat cancer and blood-related diseases.

The Food and Drug Administration has approved an initial safety study using an embryonic stem cell therapy for the treatment of serious spinal cord injuries.

What are the potential problems with using embryonic stem cells in humans?

To be useful in people, researchers must be certain that stem cells will differentiate into the specific cell types desired. Researchers, for instance, don't want to transplant a stem cell into a person hoping it'll become a heart cell only to learn that it's become a bone cell, with potentially dangerous consequences. Researchers have found ways to direct stem cells to become specific types of cells, and research into this area has advanced significantly.

Embryonic stem cells could also grow irregularly — something that's been reported in animal experiments — or travel to a part of the body where they're not intended to go. They also might trigger an immune response in which the recipient's body attacks the stem cells as foreign invaders, or simply fail to function normally, with unknown consequences. Researchers are working on ways to avoid these possible complications.

What is therapeutic cloning and what benefits might it offer?

Therapeutic cloning is a technique to create versatile stem cells independent of fertilized eggs. In this technique, the nucleus, which contains the genetic material, is removed from an unfertilized egg. The nucleus is also removed from a somatic cell of a donor. This donor nucleus is then injected into the egg, replacing the nucleus that was removed, a process called nuclear transfer. The egg is allowed to divide and soon forms a blastocyst. This creates a line of stem cells that is genetically identical to the donor's — in essence, a clone. This technique is also called somatic cell nuclear transfer.

Some researchers believe that stem cells derived from therapeutic cloning may offer benefits over those from fertilized eggs because they're less likely to be rejected once transplanted back into the donor, and they may allow researchers to see exactly how a disease develops.

Has therapeutic cloning in people been successful?

No. Researchers haven't been able to successfully perform therapeutic cloning with humans, despite success in a number of other species.

What does the future hold for stem cell therapy?

Researchers say the field has promise. Stem cell transplants using adult stem cells continue to be refined and improved. And researchers are discovering that adult stem cells may be somewhat more versatile than originally thought, which means they may be able to treat a wider variety of diseases. Studies using embryonic stem cells or embryonic-like stem cells to regenerate tissue and organs in people are just getting started. Researchers are enthusiastic about the potential for regenerative medicine treatments.

How you prepare

Pretransplant tests and procedures
Once donor stem cells become available, you undergo many tests and procedures to assess your health and the status of your condition, and to ensure that you're physically prepared for the transplant.

In addition, an intravenous (IV) catheter is typically surgically implanted, usually in your chest near your neck. This is often called a central line, and it usually remains in place for the duration of your treatment. It's through the central line that the transplanted stem cells will be infused. The central line is also used to collect blood samples, give chemotherapy, provide blood transfusions and even supply nutrition when necessary.

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

  • Destroy cancer cells
  • Suppress your immune system so that your body doesn't reject the transplanted stem cells

The type of conditioning process you undergo depends on a number of factors, including your disease, overall health and the type of transplant planned — whether you get stem cells donated from someone else (allogenic transplant) or whether the stem cells come from your own body (autologous transplant).

In some cases, the conditioning process involves high doses of chemotherapy and total body irradiation (TBI). In other cases, the conditioning process may include only high doses of chemotherapy and no radiation at all. The type of conditioning you undergo depends on your unique circumstances.

Side effects of the conditioning process can include:

  • Nausea and vomiting
  • Diarrhea
  • Hair loss
  • Mouth sores or ulcers
  • Infections, such as pneumonia
  • Bleeding
  • Infertility or sterility
  • Anemia
  • Fatigue
  • Cataracts
  • Organ failure, such as heart, liver or lung failure
  • Secondary cancers

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

'Mini' stem cell transplants
A less intense conditioning process is available through what's known as a mini stem cell transplant. It's also called a reduced-intensity conditioning transplant or a nonmyeloablative transplant.

Reduced-intensity conditioning doesn't try to kill all of the cancer cells that may be in your body. Instead, it relies on the donor's immune system cells to fight your cancer cells.

A less intense conditioning regimen may seem attractive because it may pose fewer life-threatening complications. But this kind of transplant isn't appropriate for all situations. Mini stem cell transplants are typically used only for people who can't endure the harsher conditioning regimen, such as people in poorer health, and for people whose disease isn't rapidly progressing.

What you can expect

During your stem cell transplant
Stem cell transplantation involves infusing, or injecting, donor stem cells through your central line. This usually takes one to five hours. The transplanted stem cells make their way to your bone marrow cavities, where they begin creating new bone marrow and stem cells. It can take a few weeks, though, 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 can cause. These side effects include:

  • Nausea
  • Fever
  • Chills
  • Hives

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

After your stem cell transplant
After your stem cell transplant, you may stay in the hospital until your blood counts recover or you may return home but remain under close medical care. Some people who have inpatient transplants are able to leave the hospital within three to five weeks, but others may face much longer hospitalizations. Some transplant facilities require transplant recipients to remain nearby to allow close monitoring.

In the days and weeks after your stem cell transplant, you may have many of the same kinds of tests and procedures to monitor your condition that you had before the transplant. You may also need supplemental nutrition to compensate for nausea and diarrhea.

To combat various complications, you may need to take numerous medications. 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.

Results

It usually takes about a year for your blood cells and immune system to recover to normal levels after a stem cell transplant. In general, recovery from a stem cell transplant that uses your own harvested stem cells is quicker than from one that uses donor stem cells.

A stem cell transplant can cure some diseases and put others into remission. Most people who have a stem cell transplant expect the procedure to extend their life, and it often does.

Some people sail through stem cell transplantation with few side effects and complications. Others experience numerous problems, both short and long term. The severity of side effects and the success of the transplant vary from person to person.

Most people who have a stem cell transplant and don't have a relapse of their diseases go on to enjoy a good quality of life. Many are able to return to work or school and resume their normal activities.

VIDEO :

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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.

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