1. What is an embryonic stem cell?

Embryonic stem cells are primitive cells that can be generated in a laboratory dish. Four to five days after an egg is fertilized by sperm in a dish as part of the in vitro fertilization process, the hollow microscopic ball of cells called a blastocyst forms. Scientists can remove the inner cell mass from blastocysts that cannot be used for fertility treatment and grow stem cells in a culture dish in a laboratory. Under the right conditions, these stem cells will retain the ability to divide and make copies of themselves indefinitely. Scientists are beginning to understand how to make these cells develop into any of the more than 200 different types of cells in the human body [Source: Life Sciences at University of Michigan Research].

Embryonic stem cells, as their name suggests, are derived from embryos. Specifically, embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in a dish in an in vitro fertilization clinic — and then donated for research purposes with informed consent of the donors. They are not derived from eggs fertilized in a woman's body. The embryos from which human embryonic stem cells are derived are typically four to five days old and are a hollow microscopic ball of cells called the blastocyst. Each blastocyst consists of 50 to 150 cells and includes three structures: an outer layer of cells that form the placenta, a fluid-filled cavity, and a group of about 30 pluripotent cells at one end of the cavity. This latter group of cells, called the inner cell mass, forms all the cells of the body [Source: National Institutes of Health].

Growing cells in the laboratory is known as cell culture. Human embryonic stem cells are isolated by transferring the inner cell mass into a plastic laboratory culture dish that contains a nutrient broth known as culture medium. The cells divide and spread over the surface of the dish. The inner surface of the culture dish is typically coated with mouse embryonic connective tissue cells that have been treated so they will not divide. This coating layer of cells is called a feeder layer. The reason for having the mouse cells in the bottom of the culture dish is because feeder cells release nutrients into the culture medium. Recently, scientists have begun to devise ways of growing embryonic stem cells without the mouse feeder cells. This is a significant advancement because of the risk that viruses or other contaminants in the mouse cells may be transmitted to the human cells. Because of this risk, the Food and Drug Administration greatly restricts the use of products in patients that have been exposed to animal cells or products of animal cells. Older embryonic stem cell lines are all contaminated by mouse cells and, as a result, might never be permitted to be used in patients. This is one reason scientists would like to be able to study new embryonic stem cell lines that are developed without mouse feeder layers.

Over the course of several days, the stem cells from the inner cell mass proliferate (duplicate) and begin to crowd the culture dish. When this occurs, they are removed gently and plated into several fresh culture dishes. The process of replating the cells is repeated many times and for many months, and is called subculturing. Each cycle of subculturing the cells is referred to as a passage. After six months or more, the original 30 cells of the inner cell mass yield millions of embryonic stem cells. Embryonic stem cells from a single embryo that have proliferated in cell culture for six or more months without differentiating — known as pluripotent — and appear genetically normal are referred to as an embryonic stem cell line. Once cell lines are established, or even before that stage, batches of them can be frozen and shipped to other laboratories for further culture and experimentation [Source: National Institutes of Health].

According to a survey conducted by Rand Health in 2003, there are approximately 400,000 such embryos in storage in the United States . (Source: Hoffman, D.I., et al. 2003. Cryopreserved embryos in the United States and their availability for research. Fertility and Sterility 79: 1063-1069.) Most of these embryos will never be used for fertility treatment (either because the parents are successful in having the children they want or because treatment is unsuccessful). According to the study, about two percent of these excess embryos are offered by the parents for adoption to create pregnancies in biologically unrelated mothers. Many parents are uncomfortable and unwilling to offer their excess embryos for adoption and would prefer to simply discard these embryos or to donate them for medical research that could help people. The bottom line is that there is no conflict between the adoption of embryos by biologically unrelated parents and the use of embryos for medical research: if all of the parents who prefer to put their excess embryos up for adoption do so, and all of the parents who prefer to donate their excess embryos for medical research do so, there would be more than enough embryos for both purposes.

One possible drawback to using differentiated embryonic stem cells in stem cell therapies is that embryonic stem cells from one person might be rejected by the immune system as a foreign object when placed into another person, because the proteins on the embryonic stem cell surfaces might be responded to as foreign by the recipient's immune system. For some tissues, like blood-forming cells, this is a serious problem, while in other tissues, like bone and tendons, immune rejection is not a problem. In other tissues, like during heart transplants, it is routine for patients to tolerate some degree of mismatch and to take immunosuppressant drugs to prevent rejection after transplantation.

The potential for the rejection of cells from unrelated donors applies equally to adult/tissue stem cells and embryonic stem cells. However, while adult stem cells can sometimes be isolated and then transplanted into the same patient (auto-transplants) embryonic stem cells would always be from an unrelated donor, unless they can be derived by therapeutic cloning, which is a way of making embryonic stem cells that are genetically identical to particular patients (see below). Scientists are continuing to investigate this issue to develop ways of minimizing the rejection of adult stem cells and embryonic stem cells from unrelated donors.

Embryonic stem cells have potential in many different areas of health and medical research. To start with, studying embryonic stem cells will help us understand how they transform into the broad array of specialized cells that make us what we are. Some of the most serious medical conditions, such as cancer and birth defects, are due to problems that occur somewhere during development. A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions.

Another potential application of stem cells is making cells and tissues for medical therapies. Today, donated organs and tissues are often used to replace those that are diseased or destroyed. Unfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantation. Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat a wide range of diseases, conditions, and disabilities including diabetes and Parkinson's disease. [Source: National Institutes of Health].

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