A Stem Cell Primer

What exactly are stem cells, which hold such great promise for advances in human health care, and how are they derived? Recent reports on the isolation and successful culturing of the first human embryonic stem cell lines have generated great excitement and brought biomedical research to the edge of a new frontier. The development of these cell lines deserves close scientific examination, evaluation of the promise for new therapies and prevention strategies, and open discussion of the ethical issues. To understand the importance of this discovery as well as the related scientific, medical, and ethical issues, it is absolutely essential to first clarify the terms and definitions. Stem Cell Terms * Totipotent. Stem cells, which are cells that have the ability to divide for indefinite periods in culture and to give rise to specialized cells such as blood or skin or brain tissue, are best described in the context of normal human development. Human development begins when a sperm fertilizes an egg and creates a single cell that has the potential to form an entire organism. This fertilized egg is totipotent, meaning that its potential is total--it can produce any kind of tissue found in the mature organism. In the first hours after fertilization, this cell divides into two identical totipotent cells. This means that either one of these cells, if placed into a woman's uterus, has the potential to develop into a fetus. In fact, identical twins develop when two totipotent cells separate and develop into two genetically identical human beings. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize, forming a hollow sphere of cells, called a blastocyst. The blastocyst has an outer layer of cells; inside the hollow sphere is a cluster of cells called the inner cell mass. * Pluripotent. The outer layer of cells will divide to form the placenta and other supporting tissues needed for fetal development in the uterus. The inner cell mass cells will eventually form virtually all of the tissues of the human body. Although the inner cell mass cells can form virtually every type of cell found in the human body, they cannot form an organism because they are unable to give rise to the placenta and supporting tissues necessary for development in the human uterus. These inner cell mass cells are pluripotent--they can give rise to many types of cells but nor all types of cells necessary for fetal development. Because their potential is nor total, they are not totipotent and they are not embryos. In fact, if an inner cell mass cell were placed into a woman's uterus, it would not develop into a fetus. * Multipotent. The pluripotent stem cells undergo further specialization into multipotent stem cells, which are committed to giving rise to cells that have a particular function. Examples of this include blood stem cells that give rise to red blood cells, white blood cells, and platelets; and skin stem cells that give rise to the various types of skin cells. Note that the process of changing from totipotent to pluripotent to multipotent cells is not reversible--that is, pluripotent stem cells do not produce totipotent stem cells, and multipotent stem cells do not produce pluripotent stem cells. (Figure 1.) While stem cells are extraordinarily important in early human development, multipotent stem cells are also found in children and adults. For example, consider one of the best understood stem cells, the blood stem cell. Blood stem cells reside in the bone marrow of every child and adult, and in fact, they can be found in very small numbers circulating in the blood stream. Blood stem cells perform the critical role of continually replenishing our supply of blood cells--red blood cells, white blood cells, and platelets--throughout life. A person cannot survive without blood stem cells. Pluripotent Stem Cells At present, human pluripotent cell lines have been developed from two sources with methods previously developed in work with animal models. …