Stem Cell FAQs
- What are stem cells?
- Where do stem cells come from?
- How are embryonic stem cell lines created?
- What are the potential uses of human embryonic stem cells?
- What is an embryonic stem cell line?
- What is an embryonic stem cell?
- What can be learned from human embryonic stem cell research?
- What is an adult or tissue stem cell?
- Are stem cells currently used in therapies today?
- What is the difference between therapeutic cloning and reproductive cloning?
1. What are stem cells?
Stem cells are primitive, unspecialized cells with two key properties: self-renewal (or the ability to divide and give rise to new stem cells) and the ability to undergo specialization or differentiation into the functional cells that make up tissues of the body. Stem cells are the primordial ancestors in a family tree of related cell types.
These characteristics make stem cells very promising for supplying cells to treat debilitating diseases characterized by cell loss or injury, including Alzheimer's disease, Parkinson's disease, type-1 diabetes, spinal cord injury, stroke, burns, heart disease, osteoarthritis and rheumatoid arthritis. Today, donated organs and tissues are often used to replace those that are diseased or destroyed. Unfortunately, the number of people needing transplants far exceeds the number of organs available. Stem cells offer the potential for supplying cells and tissues which can be used to treat these various diseases.
2. Where do stem cells come from?
All human beings start their lives from a single cell, called the zygote, formed after fertilization. The zygote divides and forms two cells; each of those cells divides again, and so on. About five days after conception, a hollow ball of about 150 cells called the blastocyst forms. The blastocyst is smaller than a grain of sand and contains two types of cells—the trophoblast, which form the placenta, and the inner cell mass, which will eventually give rise to all the tissues of the body. Embryonic stem cells are derived from the cells that make up the inner cell mass. Since embryonic stem cells can form all cell types in an adult, they are referred to as pluripotent stem cells.
Stem cells can also be found in very small numbers in various tissues in the adult body. To distinguish these cells from embryonic stem cells, they are referred to as "adult" or more appropriately "tissue stem cells" ("adult" stem cells are also found in fetal or pediatric tissues). Some tissues constantly undergo renewal—such as the skin, the blood system and the lining of the gut. Stem cells represent the ultimate source of cells for this ongoing process. For example, blood stem cells are found in the marrow of the bone and give rise to all specialized blood cell types such as red cells, which only live for 120 days.
Adult stem cells are typically programmed to form only cell types of their own tissue; they are called multipotent stem cells. Adult stem cells have not yet been identified in all vital organs, but we are learning more about the features and activity of stem cells in the adult. In some tissues, the stem cells only activate when there is damage or death, and their ability to respond to cell injury or damage may be inherently limited or compromised by disease. Scientists are now exploring ways in which they can induce the stem cells already present to grow and make the right cell types to replace the damaged ones.
Stem cells can also be obtained from sources like the umbilical cord of a newborn baby. This is a readily accessible source of stem cells, compared to adult tissues like the brain and bone marrow. Although scientists can grow these cells in culture dishes, they can do so only for a limited time. Recently, scientists have discovered the existence of stem cells in baby teeth and in amniotic fluid—the "water bath" that surrounds an unborn baby—and these cells may also have the potential to form multiple cell types. Research to characterize and study these cells is very promising but at a very early stage.
3. How are embryonic stem cell lines created?
Embryonic stem cells are derived from spare embryos donated by couples undergoing in vitro fertilization (IVF) treatment. In IVF, just as in natural conception, not every fertilization event results in an embryo that will develop to term. Therefore, spare embryos are routinely produced during IVF to help ensure a successful outcome. When a healthy pregnancy is achieved, the spare embryos are saved in cold storage for a period of years, after which they are discarded. If the couple agrees, however, the embryos may be used to create stem cell lines.
The spare embryo develops in a petri dish for about five days post-fertilization, at which stage it becomes a blastocyst. The blastocyst is a round ball of cells that would fit on the head of a pin. None of the specialized tissues of the body have begun to form at this stage of development, but within the ball is a small clump of cells called the "inner cell mass." These primitive cells will give rise to all the cell tissues and organs of the developing fetus. To make a stem cell line, the inner cell mass is isolated, placed in a dish in a special nutrient solution along with helper cells, and grown in an incubator at body temperature. Embryonic stem cells begin to multiply. After several weeks, the stem cell colony is divided into a number of parts that are then each placed on a new culture dish with fresh helper cells and nutrients. If the process is carried out correctly, the stem cells can be expanded indefinitely week after week for years. Throughout all of this, they retain the special property of the cells of the inner cell mass called "pluripotency," which is the ability to give rise to all cells of the human body.
4. What are the potential uses of human embryonic stem cells?
Most of the body's specialized cells cannot be replaced by natural processes if they are seriously damaged or diseased. Stem cells can be used to generate healthy and functioning specialized cells, which can then replace diseased or dysfunctional cells.
Replacing diseased cells with healthy cells, called cell therapy, is similar to the process of organ transplantation; however, the treatment consists of transplanting cells instead of organs. Some conditions or injuries can be treated through transplantation of entire healthy organs, but there is an acute shortage of donors. Stem cells can serve as an alternate and renewable source for specialized cells. Currently, researchers are investigating the use of adult, fetal and embryonic stem cells as a resource for various specialized cell types—such as nerve cells, muscle cells, blood cells and skin cells—that can be used to treat various diseases.
For example, in Parkinson's disease, a special kind of nerve cell that secretes the nerve signaling molecule dopamine is lost, leading to movement disorders. Studies have shown that if the precursors of this particular type of brain cell, obtained from fetuses following abortion, are transplanted into a patient, they will re-wire the brain and restore function.
In type-I diabetes, insulin-producing cells in the pancreas are destroyed by the patient's immune system, which confuses them for foreign invaders. This means that the patient cannot control the level of sugar in the blood, a dangerous condition that requires regular injection of the hormone insulin. Scientists have transplanted fresh pancreas cells from cadavers into patients with diabetes, and have shown that this enables the patient to live without insulin injection.
In both diseases however, the ability to use these treatments is strictly limited by the lack of availability of replacement tissue. Stem cells provide a potential solution to this limitation.
5. What is an embryonic stem cell line?
A stem cell line is a population of cells derived from a single embryo that can replicate themselves for long periods of time in vitro, meaning out of the body. These cell lines are grown in incubators with specialized nutrient and growth factor-containing media, at body temperature.
Embryonic stem cell lines, both human and mouse, can be grown indefinitely in vitro if the correct conditions are met. Importantly, these cells continue to retain their ability to form different, specialized cell types once they are removed from the special conditions that keep them in an undifferentiated, or unspecialized, state.
A very limited number of human embryonic stem cell lines have been approved for use by scientists receiving federal funds in the United States. In August 2001, President George W. Bush mandated that if scientists were using federal funds, research could only be conducted on the cell lines that were already in existence, grown from fertilized eggs that were to be discarded at in vitro fertilization clinics. This regulation stated that no additional human stem cell lines could be generated from additional blastocysts. Although the compromise policy allowed early stage studies to progress, it now places severe restrictions on scientific progress in this field.
The technology for making stem cell lines has advanced since 2001. New techniques enable us to produce stem cell lines that will be much more suitable for treating patients. Also, we know now that stem cell lines vary in important ways, and it is important to compare larger numbers of cell lines to determine which have the most desirable qualities for use in research and therapy.
6. What is an embryonic stem cell?
Embryonic stem cells are derived from the cells that make up the inner cell mass of the blastocyst. Both mouse and human embryonic stem cell lines exist. Mouse embryonic stem cells are capable of generating any and all cells in the body, under the right conditions. Therefore, they are said to be pluripotent and have unlimited potential as far as growth and differentiation. The cells divide continuously in tissue culture dishes in an incubator, but at the same time maintain the ability to generate any cell type when placed into the correct environment to cause their differentiation.
Human embryonic stem cell lines are currently being studied and several research teams are working to determine whether or not they possess the same properties as mouse embryonic stem cells. Because human embryonic stem cells were isolated relatively recently, and therefore we know less about them, it is currently more difficult to work with human systems than mouse. However, scientists are making remarkable progress that could ultimately lead to therapies to replace or restore damaged tissues using these human cells.
7. What can be learned from human embryonic stem cell research?
Apart from their potential to provide new tissues for transplantation therapy, embryonic stem cells are powerful research tools. Embryonic stem cells enable us to study early human development, and to understand the origins of birth defects and childhood cancers. We can use embryonic stem cell cultures to study human gene function in the appropriate species context, a very important capability in the post-genome era. We know what the human genome contains, but in many cases we do not know how the genes function. Human stem cells allow us to study human gene function. Finally, we can use stem cell culture to develop new medicines and study their effects on human beings. For the first time, embryonic stem cells provide us with an unlimited supply of normal human tissue. Previously, those wishing to study drug action and toxicity had to work with abnormal cell lines from human cancers, limited amounts of tissues taken directly from patients, animals or volunteer human subjects.
8. What is an adult or tissue stem cell?
Adult or tissue stem cells are distinct from cells isolated from embryos and are found in tissues that have already formed. Tissue cells can be isolated from many sources. However, in many tissues the biological role, or even the existence of stem cells, remains unclear.
In the early 2000's, many studies reported on "stem cell plasticity," a phenomenon that suggested that tissue stem cells may have a broader potential to form different cell types than was previously suspected. It was believed, for example, that cells from the bone marrow—originally thought to be purely blood-forming cells—may contribute to the regeneration of damaged livers, kidneys, hearts, lungs and other organs.
Although this field is extremely exciting, it is highly controversial in the scientific community and needs additional carefully documented research to understand the full potential of the adult stem cells, and in particular how they compare to embryonic stem cells. Many of the original studies have been hard to reproduce, or in some cases, trivial explanations have been shown to account for what was thought to be plasticity.
9. Are stem cells currently used in therapies today?
Bone marrow stem cells have been used for many years in the treatment of blood disorders including leukemias and lymphomas. Also, mesenchymal stem cells—or stem cells that develop into connective tissue, blood vessels, and lymphatic tissue—are undergoing clinical trials for several types of conditions, including joint and bone diseases. Other experimental trials of different types of stem cell are underway. While the majority of these clinical trials are carefully controlled and conducted, some unregulated clinics promise great benefits of stem cell therapy for a wide range of conditions that have not previously been amenable to treatment. It is important to consult with independent medical advisers prior to involvement in any clinical trial that has not been sanctioned by appropriate regulatory bodies, or that claims to provide striking benefits through unorthodox approaches.
10. What is the difference between therapeutic cloning and reproductive cloning?
Reproductive cloning applies cloning technology to produce a new organism that is almost an exact genetic copy of an existing or previously existing individual. Cloning of animals helps us understand basic principles of embryonic development and to efficiently propagate desired genetic characteristics, such as milk or meat production in the bovine. Therapeutic cloning is the process by which an embryo is created through nuclear transfer in order to obtain stem cells from it for therapeutic purposes.
Reproductive cloning entails removing the genetic material from a cell of the donor animal and placing it into an egg that has had its own genetic material removed. The egg is then treated by artificial means to activate it to begin embryonic development. The cloned egg cell grows and develops into an embryo. The embryo is implanted inside a surrogate mother's womb to mature and produce a viable fetus. After birth the clone would, in theory, be the genetic copy of the adult whose nucleus was used for cloning. Reproductive cloning performed in animals is burdened by many technical and biological problems. Only about one percent of all eggs that receive donor DNA can develop into normal surviving clones. In addition, the clones that survive often show many abnormalities in different organ systems. However, these abnormalities are not due to permanent genetic damage during the cloning process, because offspring of cloned animals are perfectly normal.
The entire scientific community has consistently registered its complete opposition to reproductive cloning in humans ever since the first discovery of mammalian cloning in 1997. Therapeutic cloning uses cloning technology to develop stem cells for research, and ultimately for therapy. The first steps are identical to those in reproductive cloning. A cell is taken from an accessible tissue, the skin for example, of a patient suffering from a disease, and it is then used as a nuclear donor in the cloning procedure. The patient's genetic material is transferred to a human egg from which the genetic material has been removed, and the egg is activated to begin development. However, instead of allowing the embryo to develop, the process is stopped early on. As with embryonic stem cell derivation, the inner cell mass of the five-day-old blastocyst of the cloned embryo is removed and used for the creation of an embryonic stem cell line that has the genetic makeup of the donated nucleus.
Somatic cell nuclear transfer could address important problems in research and therapy. We could use the procedure to develop stem cell lines from patients with genetic susceptibility to certain diseases, then study how the disease develops and how to treat it using stem cell cultures. Secondly, transplant rejection may pose a barrier to treatment with conventional stem cell lines. Stem cell lines derived from spare embryos are genetically distinct in patients who would receive transplants. Therefore, cells or tissues made from the stem cell cultures might be recognized by the patient's immune system as foreign, and subject to rejection.
By contrast, stem cell lines derived by nuclear transfer would provide almost a perfect genetic match for individual patients. In animal studies, cells and tissues from embryonic stem cells made by somatic cell nuclear transfer have not been rejected by the host.