Types of Stem Cells (Genetics & Inherited Conditions)
Stem cells are defined by their ability to renew themselves (that is, their ability to produce more stem cells) and their ability to diversify into other cell types. There are three major classes of stem cells: totipotent, pluripotent, and multipotent, with each of these types having progressively less developmental potential.
After fertilization, the fertilized egg (zygote) and subsequent early embryo are composed of totipotent cells, which can differentiate to become all the cells that make up the embryo, all the extraembryonic support tissues (for example, the placenta and umbilical cord), and all the cells of the adult organism. After about four days, the embryo reaches a stage of development consisting of a hollow sphere. The approximately fifty to one hundred cells on the inner side of the sphere are called the inner cell mass; these cells have lost the ability to make extraembryonic tissues and are now said to be pluripotent, and they will continue developing to form the embryo. The cells on the outer surface will give rise to the extraembryonic tissues. Importantly, the pluripotent cells of the inner cell mass are the cells scientists use to create immortalized embryonic stem cell lines. As the embryo develops, multipotent stem cells arise; these cells can self-renew but are capable of giving rise to a smaller range of differentiated cell types. For example, hematopoietic stem cells can give rise to all the types...
(The entire section is 300 words.)
Adult Stem Cells (Genetics & Inherited Conditions)
Multipotent stem cells have been identified in a wide variety of tissues in adult mammals and are specialized stem cells committed to replenishing cells of a particular function. Hematopoietic stem cells constantly replenish the blood over the life of an animal, and mesenchymal stem cells in the bone marrow give rise to bone, cartilage, fat, and connective tissue cells. Neural stem cells have been shown to give rise to neurons as well as two types of nonneuronal support cells (astrocytes and oligodendrocytes), and skin stem cells occur at the base of hair follicles and replenish the protective keratinocyte layer of the skin. Other types of adult stem cells that have been identified include liver, kidney, intestinal, retinal, muscle, dental, and pancreatic stem cells.
Stem cells in adult tissues represent only a tiny fraction of the adult cells, and thus, sophisticated techniques have been developed to identify and isolate these cells from the differentiated, non-stem cells. Adult stem cells are relatively quiescent cells, usually dividing at a slow rate to balance the loss of tissue to physiologic turnover or wear and tear. Under conditions of severe stress, adult stem cells can be induced to divide very rapidly. In the organism, adult stem cells have a practically unlimited life span; however, once isolated and cultured in a laboratory, adult stem cells are much harder to maintain in a primitive state and will ultimately...
(The entire section is 267 words.)
Embryonic Stem Cells (Genetics & Inherited Conditions)
In contrast to adult stem cells, embryonic stem cells are said to be immortalized; that is, using the right culture conditions, embryonic stem cells can be propagated indefinitely in a laboratory setting. The ability to culture and expand embryonic stem cells, coupled with their pluripotent phenotype, makes embryonic stem cell technology a powerful tool that has captured imaginations and sparked wide-ranging controversy.
Embryonic stem cells were first derived from mice in 1981 and enabled the development of technologies, such as the generation of mice defective for one particular gene, that are now fundamental and indispensable to the study of gene function and disease. In 1998, stem cell derivation techniques were successfully applied to human embryos, and the generation of human embryonic stem cells (hESC) ushered in a new era of research and controversy.
(The entire section is 131 words.)
Potential Therapeutic Uses (Genetics & Inherited Conditions)
Although stem cells have significant use as models for early embryonic development, another major research thrust has been for therapeutic uses. Stem cell therapy has been limited almost exclusively to multipotent stem cells obtained from umbilical cord blood, bone marrow, or peripheral blood. These stem cells are most commonly used to assist in hematopoietic (blood) and immune system recovery following high-dose chemotherapy or radiation therapy for malignant and nonmalignant diseases such as leukemia and certain immune and genetic disorders. For stem cell transplants to succeed, the donated stem cells must repopulate or engraft the recipient’s bone marrow, where they will provide a new source of essential blood and immune system cells.
In addition to the uses of stem cells in cancer treatment, the isolation and characterization of stem cells and in-depth study of their molecular and cellular biology may help scientists understand why cancer cells, which have certain properties of stem cells, survive despite very aggressive treatments. Once the cancer cell’s ability to renew itself is understood, scientists can develop strategies for circumventing this property.
Research efforts are under way to improve and expand the use of stem cells in treating and potentially curing human diseases. Possible therapeutic uses of stem cells include treatment of autoimmune diseases such as muscular dystrophy, multiple...
(The entire section is 392 words.)
Ethical Issues Concerning UseBioethicsstem cell research (Genetics & Inherited Conditions)
Stem cell research, particularly embryonic stem cell research, has unleashed a storm of controversy. One primary controversy surrounding the use of embryonic stem cells is the belief by its opponents that a fertilized egg is fundamentally a human being with rights to be protected. Those who oppose stem cell research object to the destruction of embryos for research purposes. Others accept the special status of an embryo as a potential human being yet argue that the respect due to the embryo increases as it develops and that this respect, in the very early stages in particular, may be weighed against the potential benefits arising from the proposed research.
In addition to the concerns over the use of embryos for research purposes, another ethical controversy arises out of the potential use of cloning techniques to produce human embryonic cell lines. Currently, hESC cells are produced from surplus embryos that have been produced for the assisted reproduction technique of in vitro fertilization. However, a potential future source of embryonic material might be embryos produced by somatic cell nuclear transfer (SCNT), also called therapeutic cloning. In SCNT, genetic material from an adult cell is fused with an enucleated egg cell. With the right conditions, this new cell can develop into an embryo from which stem cells could be harvested. Opponents argue that therapeutic cloning is the...
(The entire section is 593 words.)
Legal Status (Genetics & Inherited Conditions)
In 2001, amid much controversy, President George W. Bush issued an executive order allowing federal funds to support research on hESC lines that were already in existence but prohibiting the use of such funds to develop or work with any new hESC lines. This attempt to balance ethical considerations with potential research benefits was met with heavy criticism by both sides of the debate. In ensuing years, many states (notably California and Michigan) passed funding initiatives to support stem cell research at the state level.
In March, 2009, newly inaugurated President Barack Obama issued an executive order which largely reversed prior policy. Under the new order, federal funds can be used to support research on hESC lines if the cells in question were obtained from extra embryos created for reproductive purpose. This decision was beset by controversy as well, both by those who continue to harbor ethical objections to the use of hESC and by those who feel that the new executive order remains too restrictive. Specifically, the requirement of the new executive order for extensive documentation of the consent process for embryo donation may have the practical effect of excluding current hESC lines that were created with state or private funding that did not require the same rigorous level of documentation.
(The entire section is 210 words.)
Further Reading (Genetics & Inherited Conditions)
Cyranoski, David. “Verdict: Hwang’s Human Stem Cells Were All Fakes.” Nature 122/123 (January 12, 2006). An accounting of the controversy surrounding the fraudulent claims of Korean scientists to have created human embryonic stem cell lines using therapeutic cloning.
Holland, Suzanne, Karen Lebacqz, and Laurie Zoloth, eds. The Human Embryonic Stem Cell Debate: Science, Ethics, and Public Policy (Basic Bioethics). Cambridge, Mass.: MIT Press, 2001. A collection of twenty essays organized into four sections: basic science and history of stem cell research, ethics, religious perspectives, and public policy.
Kaji, Eugene H., and Jeffrey M. Leiden. “Gene and Stem Cell Therapies.” Journal of the American Medical Association 285, no. 5 (2001): 545-550. An overview of stem cells from a clinical viewpoint. Includes discussion of the feasibility of stem cell therapy, future research, and ethical issues.
Kiessling, Ann, and Scott C. Anderson. Human Embryonic Stem Cells: An Introduction to the Science and Therapeutic Potential. Boston: Jones and Bartlett, 2003. In the context of the social debate and public policy of the George W. Bush administration, addresses the various forms of stem cell research from the perspectives of many disciplines, from cell biology, embryology, and endocrinology to transplantation medicine.
Marshak, Daniel R., Richard L. Gardner, and David...
(The entire section is 343 words.)
Web Sites of Interest (Genetics & Inherited Conditions)
International Society for Stem Cell Research: Stem Cell Information for the Public. http://www.isscr.org/public/index.htm. Informational site from one of the leading organizations of scientists conducting stem cell research, with links to many resources.
National Institutes of Health: Stem Cell Information. http://stemcells.nih.gov/info/basics. Government site covering stem cell basics, the science of stem cell research, and links to related resources.
University of Michigan: Stem Cell FAQ. http://www.umich.edu/stemcell/faq. Site of the University of Michigan’s stem cell center, addressing stem cell basics as well as ethical issues.
(The entire section is 99 words.)
Structure and Functions (Magill’s Medical Guide, Sixth Edition)
Stem cells are unspecialized cells that can develop into all the specialized cell types that organize themselves into the tissues, organs, and organ systems making up an entire individual. An egg fertilized by a sperm is a totipotent stem cell, in that this single cell has the capacity to divide repeatedly and ultimately to contribute cells to each specialized body component. For example, from the single cell that is a fertilized human egg, cells must ultimately specialize to become the beating cells of the heart, pancreatic cells that produce insulin, skin cells that cover the body, and bone cells that support the body, among scores of other types of cells.
After fertilization, an egg divides repeatedly to form an embryo. The three- to five-day-old embryo is a hollow ball of cells called a blastocyst. Inside the blastocyst, a group of about thirty cells called the inner cell mass constitutes the stem cells of the embryo. Embryonic stem cells are referred to as pluripotent because they have the capacity to develop into most, but not all, of the specialized cell types that will form the structures needed for the embryo to develop into an adult. Embryonic stem cells do not form the placenta, the structure that provides the essential connection between mother and embryo during gestation.
Adults also harbor several types of stem cells, although a very small number in each tissue. The major function of adult stem...
(The entire section is 703 words.)
Medical Applications (Magill’s Medical Guide, Sixth Edition)
There are three major areas of stem cell research, each with potential medical applications. One branch of research seeks to discover and understand the many steps in the complex process of cellular differentiation. Other researchers are exploring the potential uses of stem cells in pharmaceutical development. A third major line of research focuses on the use of stem cells in the treatment of a host of diseases.
Embryonic stem cells are used to study the processes by which undifferentiated stem cells differentiate into specialized cell types. Through this work, scientists will gain a greater understanding of normal cell development. Understanding the mechanisms of normal cell development will provide insights into situations of abnormal growth and development. Scientists already know that turning specific genes on and off at critical times in the differentiation process is what leads to one cell becoming a muscle cell, another a lung cell, and still another a red blood cell, but the signals that influence these genes are only partially understood. Many serious medical conditions, such as cancer and certain birth defects, are the result of abnormal cellular differentiation and division. A better understanding of these processes in normal situations could lead to major insights in the development of such disorders and perhaps point the way to preventive measures or new therapeutic tools.
Established cell lines are...
(The entire section is 782 words.)
Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
In the 1960’s, researchers first discovered that bone marrow contains at least two types of stem cells. One type, termed hematopoietic stem cells, was found to form all of the different types of blood cells. The second line, termed stromal cells, generates fat, cartilage, and connective tissue. Also in the 1960’s, scientists studying adult rat brains discovered areas that contained undifferentiated cells that divided and differentiated into nerve cells. At that time, scientists did not believe that brain cells could regenerate themselves and discounted the results of this study. In the 1990’s, enough evidence had accumulated for scientists to agree that adult brains, including those of humans, contain stem cells that are able to differentiate into the three major types of cells found in the mature brain. The two main neurogenic areas of the adult mammalian brain are now known to be the olfactory bulb, which controls the sense of smell, and the hippocampus, a memory center.
Much of what scientists know about stem cells and their differentiation has come from studies in mice. The first stem cells were isolated from mouse embryos in 1981. Scientists treated these cell lines with various growth factors to stimulate the development of a particular cell type. For example, cells treated with vitamin A derivative differentiated into nerve cells. All types of blood cells and cardiac cells have been generated in similar...
(The entire section is 1065 words.)
For Further Information: (Magill’s Medical Guide, Sixth Edition)
Campbell, Neil A., and Jane B. Reece. Biology. 8th ed. San Francisco: Pearson/Benjamin Cummings, 2009. The clearly written text and informative illustrations make this introductory college textbook accessible to interested nonspecialists. The background information on cells and genetics and the introduction to stem cells will provide the reader with an excellent foundation for grasping some of the complexities of stem cell research.
Committee on Guidelines for Human Embryonic Stem Cell Research. National Research Council. Guidelines for Human Embryonic Stem Cell Research. Washington, D.C.: National Academies Press, 2005. This book provides updated information on research, regulations, and ethics of embryonic stem cell use. Of interest to scientists, physicians, ethicists, or anyone wanting to delve into this field.
Cookson, Clive, et al. “The Future of Stem Cells.” Scientific American (July, 2005). This special report from Scientific American and Financial Times synthesizes the research, ethics, politics, and commercialization of stem cells in view of potential regenerative therapies.
Holland, Suzanne, K. Lebacqz, and L. Zoloth, eds. The Human Embryonic Stem Cell Debate: Science, Ethics, and Public Policy. Cambridge, Mass.: MIT Press, 2001. The twenty essays in this book are written by scholars of biology, medicine, theology, and bioethics, among...
(The entire section is 407 words.)