Defining Stem Cells

Use of stem cells for research may provide vital clues to the treatment and cure of many of today's most serious diseases. But what exactly are they?

Joshua Tusin participated in an undergraduate research program offered through the Center for Science Education at Emory University during summer, 2001. While studying galactosemia using yeast genetics at Emory, Joshua wrote an essay that took first place in the "Science for a General Audience" category during the [link -= http://www.sciencenet.emory.edu/SURE]Summer Undergraduate Research Experience[/link] essay contest. The following article is an adaptation of Joshua's award-winning essay.

One of the hottest debates both in the media and in Washington relates to the use of stem cells. We cannot go more than a day without hearing about them in the latest news. We hear who is in favor of stem cell research, who is not in favor of research, and much more. Several groups strongly advocate either for or against stem cell use, whereas other groups attempt to stay neutral as beacons of information.

As the debate rages on, both ethical and moral issues of stem cell research arise. Advocates tout the benefits of stem cell research with the promise of curing some of our most dreaded diseases. A pro-research website, "The Why Files Guide to Stem Cells," declares that, "Once controlled and fathomed, stem cells could make drugs seem as antiquated as horseless carriages." Other groups, such as Do No Harm: The Coalition of Americans for Research Ethics, claims that, "human stem cell research requiring the destruction of human embryos is objectionable on legal, ethical, and scientific grounds." The media constantly covers these issues, particularly those focusing on the politics of stem cell research. The public is left to ponder the fundamental question underlying the whole issue: What are stem cells?

Stem cells are capable of dividing indefinitely in culture, and give rise to specialized cells. The ability to divide, or to grow, indefinitely in culture is a very important feature of stem cells. This ability to stay alive continuously makes it possible to conduct a variety of experiments, while reducing the variables within experiments. In addition, the fact that stem cells can give rise to specialized cells is key to stem cells' potential to cure diseases. Stem cells have the ability to develop into bone, muscle, cartilage, or other types of cells. The ability of these cells to develop into almost any cell type could allow for the repair of any damaged or deteriorating tissue, thus they could be used in regenerative medicine. Although it is not clear if or when such regenerative healing could be accomplished, researchers hope that stem cells can eventually be used to treat diseases such as Parkinson's disease, Alzheimer's disease, diabetes, and cancer.

Totipotent, Pluripotent, Multipotent Cells

To more fully understand stem cells, it is important to view them in the context of human development. At the time of fertilization, when the sperm and egg join, the one cell produced is capable of forming an entire organism. These cells are classified as totipotent, which means that the potential of the cell is unlimited. For a short time, each cell division creates identical totipotent cells. Any of these cells formed during the first hours after fertilization could be placed in a woman's uterus and develop into a fetus. By the fourth day, the totipotent cells begin to specialize, forming a blastocyte, or bundle of cells. The outer layer of cells form the placenta and other necessary tissues in the uterus required for the fetus to develop. The inner cluster of cells will continue to develop into nearly all of the tissues of the human body.

Although those inner cells will form virtually every type of tissue in the body, they cannot give rise to the placenta or other supporting tissues for the uterus. Thus, they are unable to form an organism on their own if placed in a woman's uterus, and are therefore referred to as pluripotent. As the pluripotent cells continue to specialize, they become cells that only lead to the development of specific tissues. Some will lead to bone marrow, while others will lead to blood or skin. The stem cells that carry this extra specialization are considered multipotent.

It is clear that multipotent stem cells play a vital role in fetal development; however, multipotent cells can still be found during the course of a person's adult life. Although usually found in very small quantities, adult stem cells play a critical role in sustaining life. For example, red blood cells are continuously replaced, and the production of new red blood cells is initiated by blood stem cells. Virtually any body function that requires growth involves stem cells. The difference between totipotent, pluripotent, and multipotent cells is essential in understanding stem cells.

Acquiring and Using Pluripotent Stem Cells

There are two initial means of acquiring human pluripotent stem cell lines, each following a protocol used with other species. The first method isolates pluripotent stem cells directly from the inner cell mass of the blastocyst. The embryos can be obtained from infertility clinics that perform in vitro fertilization (IVF). Excess embryos created for patients can be used, with consent, to harvest the inner cell mass. An alternative method of obtaining pluripotent stem cells is to culture specific cells from a terminated pregnancy. In this case, the decision to terminate the pregnancy and the consent to use the pluripotent cells are made separately. Each of these techniques yields viable and comparable stem cells lines.

Once these cells are obtained, their use is varied and vast. At a rudimentary level, these cells can offer insight into human development. Studies could be done to show how the different cell divisions take place in order to develop the variety of tissues necessary for human life. Understanding how these events occur could lead to insight on how to prevent diseases, such as cancer, that are a result of mutant cell division.

The pluripotent stem cell potential is perhaps greatest in stem cell therapy. The current need for tissue and organ transplants far surpasses the supply. Waiting lists are long and a possible solution lies in pluripotent stem cells and regenerative medicine. Since the stem cells have the ability to develop into virtually any type of tissue needed, scientists could essentially direct the cells to develop into the specific tissues required. A person needing a liver transplant could possibly receive a liver grown just for them. This technique of regeneration could be used in every division of medicine and offers hope to patients living with any number of diseases, such as Parkinson's disease, Alzheimer's disease, strokes, burns, and arthritis. Doctors would have unparalleled ability to treat and cure disease with the use of these cells.

Another use of stem cells is in the field of drug testing. All drugs go through extensive clinical trials before being tested on humans or even being considered for FDA approval. Pharmacology researchers could use stem cells to test particular drugs on a variety of cell types, in addition to testing the drugs on human cells that are in early development. Cell lines derived from cancerous cells are used in this manner, but their utility is likely to be inferior to stem cells, due to their cancerous nature. By initially using stem cells, animal testing could be reserved for later stages of drug development, when it is already known that the drug is safe in human cells. This would reduce costs both in monetary terms and lives.

In addition to the moral and ethical issues that must be addressed, a great deal of research will be needed to realize the full potential of stem cells. It is a large step to go from acquiring stem cells to actually using them in a clinical setting. Understanding the steps required for stem cell specialization is vital to learning how to direct stem cell development. Also, the stem cells acquired in the lab will be genetically different than those of a patient. This creates another obstacle to overcome: host rejection of the generated organ. Learning how to not only direct stem cell growth, but to also obtain a genetic match, is a key element to utilizing this potential application of stem cells.

Pros and Cons of Adult (Multipotent) Stem Cells

As described earlier, multipotent stem cells are derived from pluripotent stem cells. These cells have differentiated already, and will continue to specialize during development. Since these multipotent cells continue to be found in adults, they are also called adult stem cells. Multipotent cells have not yet been found for all adult tissues, but there have been and continue to be discoveries of additional adult stem cells.

The number of possible uses for multipotent cells is also quite high. Perhaps the best use of these adult stem cells would be in the field of cell transplantations. If adult stem cells can be isolated from an individual and directed to develop into a specific type of tissue, the cells transplanted into the same patient are not likely to be rejected. Additionally, making use of adult stem cells would avoid many of the ethical controversies surrounding stem cell research because aborted fetal tissue or human embryos would no longer be necessary to harvest stem cells.

Numerous limitations to adult stem cells exist, however, which pluripotent stem cells avoid. The primary issue facing researchers is whether adult stem cells can be coaxed to specialize into a different type of cell than their final tissue type. Some promise has been shown in mice and rat studies where, under certain conditions, a specialized stem cell can change its specialization. If this redirection works for human cells, blood stem cells could be coaxed to grow into nerve cells, or any other needed cell type. Further development of this research is an important task facing scientists.

Furthermore, adult stem cells have not been found for all tissues of the body, and so pluripotent stem cells are left as the only means of obtaining certain tissue types. In addition, it is impossible to obtain high quantities of stem cells from adult tissues. Obtaining adult stem cells sometimes requires significant extraction procedures.

Another limitation of adult stem cells is that stem cells from a specific patient will take time to mature in culture so that there are an adequate number of cells for treatment. This growth may take more time than available for some patients. Other times, especially when the disease has a genetic basis, the adult stem cells would likely carry the genetic error. As a further complication, adult cells are more prone to errors than younger cells. The alternative is starting with pluripotent stem cells, which are unlikely to have a defect, or finding a means of reducing the likelihood of errors in adult cells.

Scientifically defining stem cells is more complicated than it may appear, due in part to the variety of stem cells that exist. Totipotent stem cells offer comparatively little to researchers, however both the pluripotent and multipotent stem cells seem to offer great potential. These cells could be used in a variety of ways, all leading toward the treatment of diseases, many of which are currently untreatable. The moral, ethical, and political battle over stem cells will rage on, but the basics of the science stand firm. From a medical perspective, the potential of stem cells is gigantic.

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