Stem cells

Stem cells are undifferentiated cells that have the capability of self replication as well as being able to give rise to diverse types of differentiated or specialized cell lines. Stem cells are subclassified as embryonic stem cells, embryonic germ cells, or adult stem cells. Embryonic stem cells are cultured cells that were originally collected from the inner cell mass of an embryo at the blastocyst stage of development (four days post fertilization ). Embryonic germ cells are derived from the fetal gonads that arise later in fetal development. Both of these stem cell types are pluripotent, that is, they are capable of producing daughter cells that can differentiate into all of the various tissues and organs of the body that are derived from the endoderm, ectoderm and mesoderm. Adult stem cells, found in both children and adults, are somewhat more limited, or multipotent, since they are associated with a single tissue or organ and function primarily in cell renewal for that tissue.

Because they are undifferentiated, stem cells have unique properties that may make them useful for new clinical applications. Initially, stem cells were considered as a potential source of tissue for transplantation. The current standard of care for many diseases that result in total tissue and/or organ destruction is transplantation of donor tissues, but the number of available organs is limited. However, bone marrow transplantation has proven to be highly successful, and studies have shown that using blood enriched with hematopoetic stem cells leads to a higher engraftment rate than when an equivalent bone marrow sample is used. Expanding on that idea, it was hypothesized that if adult stem cells from a specific organ could be collected and multiplied, it might be possible to use the resultant cells to replace a diseased organ or tissue. One drawback to this is that adult stem cells are very rare and although they have been isolated from bone marrow, brain , eyes, muscle, skin, liver, pancreas, and the digestive system , there are many tissues and organs for which it is not known if stem cells exist. Adult stem cells are also difficult to identify and isolate, and even when successfully collected, the cells often fail to survive outside of the body. However, despite the obstacles, the theory appears to be sound, so research is continuing.

Approaching the problem from another direction, researchers hypothesized that embryonic stem cells and embryonic germ cells, under the right conditions, might be induced in vitro to produce a broad range of different tissues that could be utilized for transplantation. Research on Parkinson disease , a neurodegenerative disorder that results in loss of brain function following the death of dopamine producing cells, underscored the potential of this approach. In the 1980s, studies on monkeys and rats showed that when fetal brain tissue rich in stem cells was implanted into the brains of diseased animals, there was a regeneration of functional brain cells and a reduction or elimination the symptoms of the disease . One disadvantage to this as a clinical procedure is that random pieces of undefined tissue are used resulting in the significant possibility of variability from one patient to the next. A better solution would be to isolate the embryonic stem cells, induce these cells to differentiate, and generate a population of dopamine producing cells. Theoretically, if these cells were transplanted back into the brains of Parkinson patients, they would replace the defective cells and reverse the course of the disease. However, the mechanisms that trigger differentiation of embryonic stem cells into various specialized tissue types are not yet well understood, so it will require additional research before transplantable tissues derived from embryonic stem cells will be a reality.

In addition to possible applications in transplantation, embryonic stem cells may be useful tools in other clinical disciplines. These cells represent a stage of development about which relatively little is known. Close observation in the laboratory could provide a better understanding of normal development versus abnormal development and what triggers fetal demise. Studies on the causes and control of childhood tumors may also be possible. Embryonic stem cell lines could aid in testing the effect of new drugs and investigating appropriate drug dosages, eliminating the need for human subjects. Similarly, such cell lines may be utilized to investigate the biological effects of toxins on human cells.

It has also been suggested that embryonic stem cells might be used in gene therapy . If a population of embryonic stem cells containing a known, functional gene can be engineered, these cells might function as vectors to transfer the gene into target tissues. Once in place, the cells would hopefully become part of the unit, begin to replicate, and restore lost function. Initial studies in mice confirmed the idea was feasible. Investigators in Spain incorporated an insulin gene into mouse embryonic stem cells. After demonstrating the production of insulin in vitro, the cells were injected into the spleens of diabetic mice that subsequently showed evidence of disease reversal.

Although work is ongoing, research on embryonic stem/germ cells has generated some questions regarding the source of the cells. For research purposes, embryonic stem cells are primarily derived from leftover products of in vitro fertilization procedures. Embryonic germ cells from later gestational age fetuses have been obtained from elective termination of pregnancy or spontaneous fetal demise with appropriate parental consent. Use of such fetal tissues has posed an ethical dilemma, so new limitations on research projects have been imposed including careful review of all protocols and restriction to the use of already existing cell lines.

Although still in its infancy, stem cell research holds great promise for providing important new medical treatments in the future. There are many different diseases, ranging from heart disease to spinal cord injury and autoimmune disorders that could benefit from a better understanding of and the use of stem cells as therapeutic agents. In addition, study of these cells will impart new knowledge about human cells and early fetal development.

See also Embryo and embryonic development; Embryology; Genetic engineering; Genetics.

Resources

books

Alberts, B., et al. Essential Cell Biology New York: Garland Publishing, Inc., 1998.

Mueller, R.F., and I.D. Young. Emery's Elements of Medical Genetics. 11th ed. Edinburgh: Churchill Livingstone, 2001.

Nussbaum, R.L., et al. Thompson and Thompson Genetics inMedicine. 6th ed. Philadelphia: W. B. Saunders Co., 2001.

organizations

American Association for the Advancement of Science. "Stem Cell Research and Applications: Monitoring the Frontiers of Biomedical Research." November 1999 [cited March 10, 2003]. <http://www.aaas.org/spp/dspp/sfrl/projects/stem/report.pdf>.

other

Mayo Clinic. "Stem Cells: Medicine's New Frontier." August 10, 2001 [cited March 10, 2003]. <http://www.mayoclinic.com/invoke.cfm?id=CA00013>.

National Institutes of Health. "Stem Cells: A Primer". September 2002 [cited March 10, 2003]. <http://www.nih.gov/news/stemcell/primer.htm>.

Department of Health and Human Services. "Stem Cells: Scientific Progress and Future Research Directions." 2001 [cited March 10, 2003]. <http://www.nih.gov/news/stemcell/scireport.htm>.

University of Wisconsin-Madison. "Embryonic Stem Cells." 2001 [cited March 10, 2003]. <http://www.news.wisc.edu/packages/stemcells/index.html?get=facts#>.

Constance Stein

KEY TERMS

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Adult stem cells

—Stem cells associated with a single tissue or organ that function primarily in cell renewal for that tissue.

Differentiation

—The process whereby generalized cells change by acquiring a specific set of characters to perform a particular function.

Embryonic stem cells

—Pluripotent cells that exist in an embryo at four days post-fertilization.

In vitro

—Cells or biological processes that are present or occur outside the organism, i.e., they exist in a test tube or culture vessel.

Pluripotent

—Pertaining to a cell that has the capacity to develop into any of the various tissues and organs of the body.

Stem cells

—Undifferentiated cells capable of self-replication and able to give rise to diverse types of differentiated or specialized cell lines.

Transplantation

—Moving cells or tissues from their point of origin in one organism to a secondary site in the same or a different organism.