Stem Cells Breakthrough: Q&A

Q: Do you think that iPS cells are the only type of stem cells that will be used widely throughout the U.S. in the future, or do you think that embryonic stem cell research will continue? Anneliese , Danville, Connecticut

Daley: Dear Anneliese,
Induced pluripotent stem (iPS) cells are an exciting new form of stem cells that have enormous potential to transform biomedical research. iPS cells appear to have all of the properties of embryonic stem cells and can be made quite readily from specific patients, but iPS cells also have limitations that need to be overcome (especially the fact that we use viruses to make them). For the foreseeable future, scientists still need to study embryonic stem cells. They are the gold standard of the property we call "pluripotency"-the capacity to morph into any tissue in the body. iPS cells were discovered as a direct consequence of studying pluripotency in embryonic stem cells. At the very least, we will need years to learn how similar and different iPS cells are compared to embryonic stem cells.

If I look into the future, I predict that scientists will be studying many different forms of stem cells-embryonic, iPS, stem cells from specific tissues (called "somatic" or "adult" stem cells), and forms yet to be discovered. For biomedical scientists, the only means of answering important questions about how the earliest tissues form in humans is to continue to study embryos and how embryonic stem cells form.

Q: Can you use stem cells from a fetus that is born alive? If you can, why is there so much fuss about it? Or must you abort the baby to get the stem cells? Please clear this up for me. Thanks. Janet, Canton, Ohio

Daley: Dear Janet,
Stem cells can be isolated from several sources. Human embryonic stem cells are isolated from the earliest human embryos, which are created through in-vitro fertilization but are in excess of what the couples need for family building. Rather than discard these embryos as medical waste, couples can donate them to medical research. At the stage when human embryonic stem cells are isolated, the embryo is called a pre-implantation blastocyst. It is a few days old, comprised of a ball of a few dozen to a hundred or so cells, is smaller than a period at the end of a sentence, and if found naturally inside a woman's body, would not yet have attached itself to the wall of the womb. Thus virtually all human embryonic stem cells in use today are made from the earliest human embryos created in the test tube and are not associated with abortion.

A fetus develops within a woman after several weeks of pregnancy. Some women who have chosen abortion have donated the fetal tissue to medical research. The tissues have been used in research aimed at treating Parkinson's disease, and in a few cases have been used to generate stem cells called embryonic germ cells, which behave very much like embryonic stem cells.

If I look into the future, I predict that scientists will be studying many different forms of stem cells-embryonic, iPS, stem cells from specific tissues (called "somatic" or "adult" stem cells), and forms yet to be discovered. For biomedical scientists, the only means of answering important questions about how the earliest tissues form in humans is to continue to study embryos and how embryonic stem cells form.

Q: I have two questions:

1) What is it that differs between the iPS cells and embryonic stem cells that causes iPS cells to be less pluripotent?

2) What exogenous factors do researchers utilize to differentiate stem cells into the type of cells they are interested in? Jason Kwon, Crawfordsville, Indiana

Daley: Dear Jason,
In regard to your first question, scientists are still curious about the similarities and differences between iPS cells and embryonic stem (ES) cells. In mice, we can compare the two types of stem cells in the most stringent and thorough ways, which typically involve injecting the cells back into early mouse embryos to see if the implanted cells will contribute to all of the tissues as the mouse develops. In these studies, iPS cells have behaved almost equivalently to ES cells, but scientists are quite interested in the tiny, most subtle differences. Scientists are beginning to appreciate that different strains of iPS cells may be more variable than ES cells, and that iPS cells may not form certain tissues in the Petri dish as well as ES cells. But all of these studies are still very preliminary, and in the future, we hope that scientists will be able to create iPS cells that are indistinguishable from ES cells.

In regard to your second question, scientists use a wide range of tricks to coax stem cells to become specialized, or "differentiated," into specific cells and tissues. For instance, to make embryonic stem cells turn into blood, scientists add proteins called cytokines that are available as drugs to stimulate production of red and white blood cells in patients undergoing chemotherapy. To make neurons, scientists add a variety of chemicals like retinoic acid that are known to regulate the formation of the brain and spinal cord. In most cases, scientists are guided by principles first discovered through studies of animal and human development. The goal is to drive stem cells to become specialized into specific tissues by recreating the same conditions in a Petri dish that exist as our bodies form during gestation. In some cases, scientists take a trial-and-error approach, and simply add large numbers of chemicals to many, many tiny vials of cells, then observe which cells turn into the tissues they are looking for. This unbiased approach to "screening" of large libraries of chemicals, long used by the pharmaceutical industry to discover new drugs, may ultimately prove to be the most productive.

Q: My co-worker's seven-year-old son has just been diagnosed with Diabetes I. Do you think stem cell research will bring him a "cure" during his lifetime? Linda Pharis , Roanoke, Virginia

Q: How much longer do you anticipate it will be before we see a stem cell related cure for diabetes? I've had it since 1967, but I still have hope. Anonymous

Daley: Diabetes is a terrible disease, especially when it strikes little kids, and despite treatment with insulin, diabetics suffer many health problems over the long run. In many patients with diabetes, and most cases of the juvenile form, the very cells that produce insulin in the pancreas (the beta cells) deteriorate or are attacked by the body's immune system, and the best means of restoring health and effecting a cure would be to replace that missing tissue. Therefore one of the ambitions of stem cell research is to figure out how to make stem cells form insulin-producing beta cells in a Petri dish. The hope would be that the beta cells could then be transplanted back into the diabetic patient, restoring their ability to produce insulin and regulate sugar in the blood, thus eliminating the need to inject themselves with insulin shots. Alternatively, studying how insulin-producing beta cells form in the test tube from stem cells might allow scientists to find drugs to enhance the survival or regeneration of the few beta cells that might still exist in the diabetic pancreas.

Diabetes research is one of the most exciting and promising areas of stem cell research. I wish I could give you an estimate of when a cure would be available, but scientific discovery is impossible to predict. I think the probability is high that we will see major new treatments being tested in patients within a decade, but that might be optimistic and I don't want to over-promise and create false hope. Stay tuned, and let's all wish for the best.

Q: If stem cell research leads to a cure for sickle cell anemia, would such a treatment be pretty much directly applicable to cystic fibrosis as well? Ralph Hoover, Topeka, Kansas

Q: Hello, I was told to watch your program on stem cell breakthrough; I have sickle cell anemia and type 1 diabetes too. Is there really a cure for sickle cell anemia, and how long do I have to wait for a major breakthrough? Kim, New York

Daley: Dear Kim and Ralph,
The NOVA scienceNow piece highlighted the very exciting research breakthrough from the laboratory of Professor Rudolf Jaenisch, one of the world leaders in stem cell research. Dr. Jaenisch's lab succeeded in treating a mouse that had been engineered to have the human disease sickle cell anemia, using methods that would not yet be safe enough to try in humans. My own laboratory and many others around the world are actively focused on translating this exciting research into human stem cells and human patients, but much work remains before we could imagine attempting clinical trials in real patients like you.

The basic methods described by Dr. Jaenisch are applicable to a whole range of human diseases, especially those where we know the specific gene defect, like sickle cell anemia and cystic fibrosis. But each disease condition has unique features and challenges, and some will be ready for clinical testing before others. Because doctors already have so much experience transplanting blood stem cells between healthy donors and patients, there is hope that treatment of genetic blood conditions will be among the first to be attempted in human clinical trials.

Q: Can stem cell research be used on HIV-positive and AIDS patients like myself to be free of the virus? I would volunteer my cells.

Thank you. Anonymous

Daley: HIV infects blood cells and cripples the immune system. The entire immune system and all blood cells arise from a single type of cell called the hematopoietic stem cell. Research into the hematopoietic system-the best understood of all stem cell systems-has produced many insights about HIV and AIDS: how immune cells form from stem cells, which specific cells within the blood are susceptible to infection by the AIDS virus, and how treatment with powerful anti-retroviral drugs allows the immune system to regenerate from stem cells. Some strategies envisioned for eradicating the AIDS virus involve replacing infected blood cells in patients with HIV-resistant hematopoietic stem cells. I suggest you keep a watchful eye on AIDS research, and a good resource is the National Library of Medicine website: http://sis.nlm.nih.gov/hiv.html.

Q: To your knowledge, at the stage it is now, is there or could there be limits to the types of ailments stem cells could cure, and if so, what kinds of ailment/sickness? Daniel Tremblay, Montreal, Quebec, Canada

Daley: Dear Daniel,
Stem cells are not a panacea for all ills, but because stem cells are the foundation of repair and regeneration in so many different tissues, stem cell research has the broad potential to contribute to basic knowledge in many different disease conditions. There will ultimately be some conditions that can be treated by stem cells or the fruits of stem cell research, and others that will not. The diseases most likely to benefit from stem cell research and treatment are diseases affecting the blood (like sickle cell anemia, immune deficiency, and leukemia), diabetes, neurodegenerative conditions like Parkinson's, and rare disorders like congenital blindness.

Q: Has there been any progress in stopping pluripotent stem cells from proliferating to avoid the potential risk of tumor formation? Robin Walenius, Loxahatchee, Florida

Daley: Dear Robin,
As your question correctly implies, pluripotent stem cells (both iPS and ES) share some features with cancer cells. They are immortal and will grow forever in culture, and they can produce tumors called teratomas. Thus, treating diseases with differentiated products of pluripotent stem cells carries a risk that some residual undifferentiated stem cells will contaminate the tissue grafts and lead to tumor formation. Scientists are well aware of this danger, and will purify differentiated tissue cells to eliminate the pluripotent stem cells from cell products prior to treating patients. Scientists might also engineer stem cells with "suicide pills" prior to transplanting patients, so that transplanted cells can be eliminated if they become renegades.

Before stem cells can be used in therapies, many safety issues must be addressed. But clinicians and patients must remain wary as we move towards clinical trials, because in addition to the risk for tumor formation, stem cells may cause adverse side effects that we cannot yet even anticipate.

Q: What kinds of laws prohibit us from cloning cells or whole organisms? Chris Deshon, Maryville, Illinois

Daley: Dear Chris,
In the United States, there are no federal laws that prohibit reproductive cloning-producing babies using a procedure called somatic cell nuclear transfer. However, many states have outlawed human reproductive cloning, and every major scientific organization that represents stem cell researchers has called for prohibitions on human reproductive cloning.

What scientists wish to preserve, however, is the freedom to create genetically identical copies of a patient's cells-which uses the same techniques of somatic cell nuclear transfer but with the intent of cloning cells, not babies. Cloning of animals proceeds as a valuable means of creating goats, cows, and sheep that can manufacture medicines or provide for a safer food supply (e.g., by producing cows that are resistant to mad-cow disease and hence produce safer meat).

Q: Dear Dr. Daley,
Is it possible to use stem cells in order to repair a spinal cord that was damaged by accident and thereby help many victims who are otherwise powerless and in wheelchairs the rest of their lives? Why does it take so long to find a therapy when cardiologists already use stem cells to "repair" heart damage?

Thank you. Anonymous

Daley: The world's first human clinical trial using human embryonic stem cells may indeed be to test the safety of such cells in patients with spinal cord injury. While animal experiments appear promising, spinal cord injury represents an enormous challenge and these trials may prove safe but ineffective. Only time will tell.

It is important for patients to appreciate the difference between early clinical trials that report provocative positive results and the time-tested therapies that become accepted standards of medical care. Many experimental treatments appear very promising in early clinical trials and yet fail when tried in larger numbers of patients. Except for treatments for blood conditions like leukemia, all stem cell therapies are highly experimental in nature and none have proven themselves worthy of being considered a proven treatment. Some but not all studies of heart treatments have produced modest improvements. Patients must remain wary of claims of treatment success that are all over the internet. Patients should not be mislead to believe that their condition can be cured with stem cells, and they certainly should not be traveling great distances and paying large sums of money to be administered unproven treatments. Given today's knowledge, the risk of harm is likely far greater than the risk of benefit.

Q: Do you think there is an element of consciousness within each living cell? And if yes, could your research show that consciousness is more developed in stem cells? June-Elleni Laine, London, U.K.

Daley: Dear June-Elleni,
This is a fascinating philosophical question that raises provocative issues about the nature of "life" and the distinctions between the "life" within a cell, and the "life" of an organism. If you mean by consciousness the awareness of one's surrounding, then as a biologist I am confident that single cells do indeed sense their environments and react and adapt to them. The cell is alive and has a very primitive form of consciousness. But this competence to sense the environment at a single cell level is quite distinct from what is possible at the organismal level, where whole organ systems have evolved to sense and react to the environment. This level of consciousness-called sentience-is an integrated property of experience and interpretation that requires a brain and a nervous system. As such, only organisms can be sentient; only organisms can think and form emotions and experience pain. Much of the debate surrounding stem cell research hinges on when "life" begins. To a biologist, single cells are alive, but due to the different nature of consciousness single cells do not command the same level of reverence as sentient beings. When the early human form is an embryo consisting of a ball of cells in a Petri dish, most bioethicists feel that it is justified to use them for research.