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Caption: Microscopic view of a colony of original human embryonic stem cell lines from the James Thomson lab at the University of Wisconsin-Madison. These cells, which arise at the earliest stages of development, are blank slate cells capable of differentiating into any of the 220 types of cells in the human body. They can provide access to cells for basic research and potential therapies for many types of disease. Thomson, a developmental biologist and professor of anatomy, directed the research group that reported the first isolation of embryonic stem cell lines from a nonhuman primate in 1995, work that led his group to the first successful isolation of human embryonic stem cell lines in 1998. In 2007, Thomson and his colleagues, and a group in Japan, successfully reprogrammed adult skin cells to create the world’s first induced pluripotent stem cells, cells that have all the qualities of embryonic stem cells.
Date: 2005
Photo credit: Jeff Miller/University of Wisconsin-Madison

The Mayo Clinic – 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 struggle with understanding 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, you can sort through the hype and the hope and get answers to frequently asked questions about stem cells.

Why is there high interest in stem cells?

Researchers are interested in stem cells for two main reasons:

* Knowledge. By studying how stem cells mature into cells that eventually become bones, heart muscles, other organs and tissue, researchers hope to learn more about the function of stem cells and what can go wrong in development. This knowledge may shed new light on how a variety of diseases and conditions develop, such as heart disease, cancer or birth defects.
* Therapy. Researchers hope they can manipulate stem cells into becoming specific types of cells. If this is done successfully, stem cells may be used to regenerate and repair tissues and organs to treat diseases and conditions such as diabetes, heart failure, Parkinson’s disease, inherited genetic diseases or spinal cord injuries. Stem cells could also be grown to become organs to use in transplants, since donor organs are often in short supply. Stem cells may also one day be useful in testing experimental medications before human clinical trials.

What exactly are stem cells?

Stem cells are master cells of the body — cells from which all other cells with specialized functions are created. 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 ability to self-renew or to differentiate.

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Caption: This microscopic image shows a large sphere of neural stem cells in culture, surrounded by stem cells that are “leaving home,” migrating away from the sphere. To better address the public issues raised by new neuroscience research, two University of Wisconsin-Madison faculty, professor of neuroscience Ronald Kalil and professor of science and technology policy Clark Miller, have created a new dual-degree graduate program in neuroscience and public policy.

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 50 to 150 cells. These are pluripotent (ploo-RIP-o-tunt) stem cells, meaning they can divide into more stem cells or they can specialize and become any type of body cell. In this way, 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 for these cells is somatic stem cell, meaning “of the body.” Until recently, it was felt 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, a controversial new theory 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 is in the very early stages.
* Adult cells altered to have properties of embryonic stem cells. In late 2007 two groups of researchers reported they had created stem cells from skin cells in laboratory studies. By altering the genes in the skin cells, researchers were able to reprogram the cells to act similarly to embryonic stem cells. While this new technique may help researchers avoid the controversies that come with embryonic stem cells, more research is needed. The technique of altering adult cells involves processes that may not be safe for use in people. And whether this new type of stem cells can be as useful as embryonic stem cells remains to be seen.
* Embryonic germ cells. These are stem cells that come from areas within an embryo or fetus that are destined to become either the testicles or ovaries. Like embryonic stem cells, embryonic germ cells can become any type of cell. Less research has been done on embryonic germ cells because the embryos used to obtain them must be aborted. In addition, these cells tend to differentiate spontaneously, so they may be more difficult to use in a controlled manner.
* 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 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 is generally considered safe for the developing fetus and the mother. Researchers were able to use amniocentesis fluid to identify stem cells that could develop into several other types of cells. More study of amniotic fluid stem cells is needed to understand their potential.

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 the embryos destroys the embryos. Some people view this as taking a human life, which raises moral and ethical considerations.

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.

Researchers believe that 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.

What is a stem cell line 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 dividing 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. This way, researchers don’t have to get stem cells from an embryo itself.

Why do researchers want to create more embryonic stem cell lines?

Researchers who receive federal funding to support their experiments — as most academic researchers do — are limited by law to working with about 20 stem cell lines. Those who want to experiment using other stem cell lines must find private funding for separate laboratory space and private funding must also be used to buy separate equipment for research.

The 20 or so stem cell lines approved for research date back to the late 1990s, and some researchers contend that they pose several problems:

* The limited number of stem cell lines limits the genetic diversity available, so cells may be useful only for certain diseases or people.
* The lines are old, so cells don’t grow as well as new ones.
* The lines may have been contaminated by nonhuman cells in the growth cultures, compromising their safety.
* The DNA in some of the cells may subtly change over time, causing genetic flaws that could be passed along to daughter cells or to humans.

How can additional stem cell lines be made available more quickly to U.S. researchers?

It will take a presidential order or an act of Congress signed by the president to make federal funding available for research on other stem cell lines. This would speed the development of embryonic stem cell research in the United States.

Some researchers have turned to private funding to finance their embryonic stem cell studies and have created their own stem cell lines. Also, individual states can pass their own laws allowing funding of embryonic stem cell research with state money.

What is stem cell therapy and how does it work?

Stem cell therapy is the replacement of diseased, dysfunctional or injured cells with either adult or embryonic stem cells. It’s somewhat similar to the organ transplant process but uses cells instead of organs. Stem cell therapy is sometimes called regenerative medicine.

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 are then implanted into a person. If the person has heart disease, the cells would be injected into the heart muscle. The normally functioning implanted heart cells, in theory, could replace the defective heart cells.

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 have proved highly successful in treating a number of cancerous diseases, such as leukemia, and noncancerous diseases, such as aplastic anemia.

Stem cell transplants use cells harvested from a donor’s or person’s own bone marrow, circulating blood or umbilical cord blood. These are all adult stem cells. In addition, adult stem cells have been used in human experiments testing the potential treatment of diabetes, heart disease and other conditions.

Embryonic stem cell treatment is just beginning to be tested in people. Clinical trials using stem cells to treat neurological diseases are the first to begin recruiting participants.

To be useful in people, researchers must be certain that embryonic 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 continues.

Embryonic stem cells could also become tumor cells — something that’s happened 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 have found ways to avoid these complications and continue studying ways to control stem cells.

What is therapeutic cloning and what benefits might it offer?

Therapeutic cloning is a technique to create embryonic stem cells without using fertilized eggs. In this technique, the nucleus is removed from a woman’s unfertilized egg. The nucleus is also removed from a somatic cell of a donor — a person with a disease or injury, such as type 1 diabetes. 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 embryonic 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 embryonic 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.

In addition, some researchers consider therapeutic cloning a good alternative to creating embryonic stem cell lines from fertility treatments, since they come from cells that were never fertilized. However, this technique is not without opponents. Critics contend therapeutic cloning can also be perceived as destruction of a human life or potential human life.

Has therapeutic cloning in people been successful?

Researchers haven’t been able to successfully perform therapeutic cloning of humans. In 2005, South Korean researchers reported creation of human embryonic stem cells this way, but their claims were ultimately not substantiated.

What does the future hold for stem cell therapy?

Researchers say the field has great 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 to regenerate tissue and organs in people are just getting started. Researchers are enthusiastic about the potential for these treatments.

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Caption: Red blood cell colony derived from human embryonic stem cells by scientists at the University of Wisconsin-Madison. These are the first specialized human cells coaxed down a specific developmental pathway to be reported in the scientific literature. The ability to make human blood in the lab may one day augment human blood supplies for purposes of transfusion and transplantation.
Date: 2001
Photo credit: UW-Madison University Communications 608/262-0067
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Caption: Derived from human embryonic stem cells, precursor neural cells grow in a lab dish and generate mature neurons (red) and glial cells (green), in the lab of University of Wisconsin-Madison stem cell researcher and neurodevelopmental biologist Su-Chun Zhang.

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