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Stem Cells: Medicine’s New Frontier

Wednesday October 20, 2004

Mayo Clinic staff

October 13, 2004(MayoClinic.com) - Medical researchers are working hard to discover the secrets and healing potential lurking inside your stem cells. These cells, unlike other cells in your body — such as your skin cells or muscle cells — do more than perform a specific function. They have the ability to produce the many different types of cells and tissues that make up your body. This unique quality means that these cells, if properly controlled, might someday treat a range of conditions — from baldness to spinal cord injuries — by replacing damaged or diseased cells.

More importantly, as scientists learn more about stem cells, they also gain a better understanding of how embryos develop all the cells, tissues and organs needed to sustain life. And they learn more about how certain diseases and conditions develop.

However, stem cell research is a very young field of study. Although stem cells already have some practical applications, scientists must overcome a number of obstacles before they learn how best to use these cells to improve your health.

What are stem cells?

Stem cells are your body’s basic building blocks. Certain qualities make them unique from other cells in your body. Stem cells are: Undifferentiated. As undifferentiated cells, stem cells don’t have a particular function — the way cells in your arm muscles that help you lift a package or cells in your blood that carry oxygen do. Instead, stem cells are like neutral observers waiting to be pressed into duty. Although they’re undifferentiated, they can turn into specialized cells. Imagine that you’re repairing a home and you have a substance that you can transform into any material you need throughout the house — from carpet to paint to shingles. This unique substance could be used to fix many different problems. Stem cells may be useful in repairing various parts of your body in this way. Self-replicating. Unlike other cells in your body, which don’t typically produce copies of themselves (replicate), stem cells can divide and replicate over and over again. In the laboratory, stem cells can replicate over long spans of time without becoming specialized. Researchers can grow such unspecialized cells in a laboratory dish, then separate groups of them away and start new batches of dividing cells until they have millions of cells. This allows scientists to produce plenty of unspecialized cells for study — and possibly for future use in medical treatment.

Stem cell replication When a stem cell divides, it creates a stem cell that’s specialized ...

Types of stem cells: From embryos to adults Not all stem cells are created equal. The potential for stem cells to differentiate into other specialized cells changes as an embryo develops.

Stem cells can be:

Totipotent. In the early stages after fertilization — immediately after a sperm and egg join together and begin dividing — stem cells are considered totipotent. This means that these cells can form any type of cell, including those cells necessary for an embryo to develop into a human, such as placenta cells.

Pluripotent. Several days after conception, as an embryo begins to develop, its stem cells become pluripotent. Such cells can form any kind of cell found in adults, making them very versatile. Unlike totipotent stem cells, however, they can’t become cells necessary for an embryo to develop into a human. Cells with similar properties are also found in fetal tissue.

Multipotent. Eventually, pluripotent stem cells become multipotent stem cells — the type found in adults. Multipotent stem cells can no longer develop into all or most cell types. Instead, they can develop into certain cell types within a specific tissue, organ or system. For example, bone marrow stem cells can develop into all types of blood cells, which are normally produced by your bone marrow, as well as bone, cartilage and fat cells. Stem cells in your brain can turn into nerve cells and other types of brain cells.

Multipotent stem cells exist in certain tissues and organs throughout your body, including your brain, blood vessels, liver, muscles and bone marrow. Researchers believe that multipotent cells remain — undivided — in these parts until they’re called into duty to create necessary new cells, such as after a disease or injury.

Some scientists suspect that stem cells in one body part may be able to form cells used in other body parts, a quality called plasticity. For example, a stem cell in your bone marrow that makes blood cells might also be able to make heart-muscle cells or liver cells. Stem cells in use: Current treatments Although they’re not a cure for any condition, stem cells can assist in the treatment of certain conditions. Despite the fact that stem cell research is still in its relative infancy, doctors have used stem cells in bone marrow transplants for more than 30 years. Bone marrow contains blood-forming stem cells. These cells continuously produce oxygen-carrying red blood cells, white blood cells that help fight infection and platelets that help stop bleeding. Bone marrow and stem cell transplants help treat certain cancers, such as leukemia and lymphoma, and some noncancerous conditions, such as aplastic anemia and some inherited immune disorders. Researchers are also investigating their use in some breast and ovarian cancers.

Aplastic anemia Leukemia Non-Hodgkin’s lymphoma

The chemotherapy and radiation used to treat these diseases can destroy bone marrow, leaving your body unable to produce the new blood cells you need to carry oxygen throughout your system and to fight infections. Stem cell transplants — though not a cure for the cancer itself — provide you with new cells that can regenerate the bone marrow.

The first bone marrow transplants gave bone marrow from a healthy relative to a person affected by a bone marrow disease. These transplants, called allogeneic transplants, are riskier than are transplants using the person’s own bone marrow. More recently, for some diseases, bone marrow transplants have used a person’s own marrow after it is removed from bone, treated and frozen. Chemotherapy and radiation treatments destroy the cancer cells or defective material in the removed marrow, and the remaining healthy marrow is transplanted back into the individual. Today, the treatment commonly involves using blood — as some stem cells also circulate in the bloodstream — rather than marrow. This is known as peripheral blood stem cell transplantation.

What lies ahead: Possible uses Potential uses for stem cells could someday extend far beyond bone marrow and blood transplants. Stem cells may help to: Replace diseased cells. If scientists can harness stem cells’ ability to become specialized into any type of cell, they may be able to use them to treat any number of diseases and conditions. For example, Parkinson’s disease — a condition marked by tremors and loss of muscle control — is caused by the loss of certain brain cells that create the chemical dopamine. Stem cells could potentially be used to replace such cells. In fact, Parkinson’s may be one of the first diseases to be treated with stem cells, since experts have already prompted embryonic stem cells to specialize into cells similar to the dopamine-creating cells.

Stem cells may also prove to be helpful in treating type 1 diabetes. With this disease, islet cells in the pancreas, which produce a crucial hormone called insulin, are damaged. Doctors could someday prompt stem cells to form new, healthy islet cells, then inject them into the liver of a person who has diabetes. This may eliminate the need for insulin injections, which are typically necessary to manage type 1 diabetes.

Healthy cells provided by stem cell transplants may one day help treat a variety of other conditions as well. These could include Alzheimer’s disease, spinal cord injuries, liver disease, arthritis and hair loss. Form new tissues. Stem cells injected into a diseased organ — such as a failing heart — may also one day help keep an organ functioning. They may even be used to grow a new organ. This would give a second chance to people who are waiting for organ transplants for which available organs are in short supply. Develop new medications. If researchers could use stem cells to generate specific types of cells found in the body, they might test the safety of new drugs on those resulting cells.

Learn about cancer and birth defects. By learning more about how stem cells divide and differentiate, researchers may increase our understanding of cancer and birth defects, conditions marked by improper cell growth and differentiation.

Organ transplantation: Coping with the wait

Obstacles facing stem cell research Reaching the point where society can reap the potential benefits of stem cells will take time. Researchers face a number of major challenges as they study stem cells.

Technical hurdles Controlling stem cells isn’t easy. Both adult and embryonic stem cells present challenges. Though stem cells exist in adult tissue, they’re not present in great numbers, so they can be hard to find and to extract for growth. They also may be difficult to grow into large batches of unspecialized cells in the laboratory — a necessary step if they’re to serve as replacement cells in disease treatment. And their ability to transform into different kinds of cells appears to be limited.

Working with embryonic stem cells has its challenges, too. Though they’re easier to grow into batches of unspecialized cells, scientists need to better understand how these cells reproduce in the laboratory, and how to reliably trigger them to differentiate into the specific types of cells needed. Concerns that transplanted stem cells may not work in conjunction with the tissue of the person receiving them also exist. Transplanted cells could "overgrow," as happens in many cancers. And a person’s immune system may reject the cells as foreign, because cells derived from embryonic or fetal tissue are genetically different from mature tissue.

Ethical questions Because of the technical limitations involved in using adult stem cells, embryonic stem cells are generally more appealing to stem cell researchers. But the use of embryonic stem cells gives rise to ethical questions.

Embryonic stem cells are derived from embryos created outside of a woman’s body (in vitro) — using donated eggs fertilized in a laboratory — not from eggs fertilized inside a woman’s body. Gathering embryonic stem cells requires destroying the embryo. Some people believe this process represents a destruction of human life, and feel that it shouldn’t be done for research purposes. Others disagree, suggesting that an embryo doesn’t have the same rank as a fetus. Some believe it’s OK to use embryos for research if they’re not being created specifically for research, but instead exist as unused byproducts of an in vitro fertilization procedure for infertile couples.

Infertility Even more ethical issues are raised when cloning enters the discussion. Some scientists have obtained embryonic stem cells using a process known as therapeutic cloning. During this process, scientists replace the nucleus of an egg cell with the nucleus from another cell in the body to grow an embryo from which to harvest stem cells with specific properties, such as a new gene. This process differs from reproductive cloning, during which an egg is given the new nucleus and implanted into a woman’s uterus so it will grow into a full-term fetus.

Legal limitations Laws in the United States also place limitations on the use of embryonic stem cells for research. In 2001, an executive order limited federal funding for research on human embryonic stem cells.

This order means that if funded by federal money — as many research studies are — a scientist can only work with a limited number of already existing human stem cell lines that meet certain criteria. A stem cell line is a group of cells that can self- replicate outside the body for an extended period of time. Stem cell lines are appealing to scientists because the lines can be grown and shared indefinitely, eliminating the need to go through the difficult process of isolating and obtaining the stem cells again.

The allowable stem cell lines originated from embryos that already existed for reproductive purposes and were no longer needed for those purposes. Those who donated these embryos weren’t paid for them and consented to their use in research.

Working exclusively with these stem cell lines presents some challenges for researchers. The number of available lines is limited. Some researchers question the quality and genetic diversity of the lines. Many of these cell lines have been exposed to animal-derived substances, which may increase the risk of certain infections. And, because private parties developed the lines, they don’t have to share them and can charge researchers any amount they choose.

In March 2004, a group of scientists announced the existence of 17 new stem cell lines developed with the use of private funds. They plan to share these lines with other researchers. But research funded by government monies can’t use these lines because they aren’t derived from embryos that existed prior to the 2001 executive order.

The great unknown Much remains to be learned about stem cells, including potential hazards. Real applications, for the most part, are still years away. But if progress with blood and bone marrow transplants is any indication, stem cell research may someday help many people. These tiny cells may significantly advance disease treatment and expand human knowledge of the body’s basic processes.