Also found in: Dictionary, Thesaurus, Medical.
stem cells,unspecialized human or animal cells that can produce mature specialized body cells and at the same time replicate themselves. Embryonic stem cells are derived from a blastocyst (the blastula typical of placental mammals; see embryoembryo
, name for the developing young of an animal or plant. In its widest definition, the embryo is the young from the moment of fertilization until it has become structurally complete and able to survive as a separate organism.
..... Click the link for more information. ), which is very young embryo that contains 200 to 250 cells and is shaped like a hollow sphere. The stem cells themselves are the cells in the blastocyst that ultimately would develop into a person or animal. "Adult" stem cells are derived from the umbilical cord and placenta or from blood, bone marrow, skin, and other tissues. The similar embryonic germ line cells come from a fetus that is 5 to 9 weeks old and are derived from tissue that would have developed into the ovaries or testes.
Medical researchers are interested in using stem cells to repair or replace damaged body tissues because stem cells are less likely than other foreign cells to be rejected by the immune system when they are implanted in the body. Embryonic stem cells have the capacity to develop into every type of tissue found in an adult; germ line cells and adult stem cells are less versatile. The processes that control such development, however, are not understood at present. Stem cells have been used experimentally to form the hematopoietic (blood-making) cells of the bone marrow; heart, blood vessel, muscle, tracheal, retinal, and insulin-producing tissue; bone; and sperm cells. Embryonic germ line cells have been used to help paralyzed mice regain some of the ability to move. Since the 1990s umbilical cord blood stem cells have sometimes been used to treat heart and other defects in children who have rare metabolic diseases and to treat children with certain anemias and leukemias. It has been shown that stem cells from this blood can migrate to damaged tissues and repair them.
Human stem cells have typically been extracted from surplus fertilized embryos produced during in vitro fertilizationin vitro fertilization
(IVF), technique for conception of a human embryo outside the mother's body. Several ova, or eggs, are removed from the mother's body and placed in special laboratory culture dishes (Petri dishes); sperm from the father are then added, or in many cases a
..... Click the link for more information. procedures. Some experimenters, however, have used embryos that were fertilized especially to produce stem cells. In so-called therapeutic cloning a nucleus from a patient's body cell, such as a skin cell, would be inserted into an egg that has had its nucleus removed to produce a blastocyst whose stem cells could be used to create tissue that would be compatible with that of the patient. Such a procedure was reported in 2005 to have been successfully undertaken in part by South Korean researchers who produced stem cell lines using genetic material from patients, but the data was subsequently shown to have been fabricated. (It was later determined, however, that the laboratory had produced stem cells using an egg that had developed through parthenogenesisparthenogenesis
[Gr.,=virgin birth], in biology, a form of reproduction in which the ovum develops into a new individual without fertilization. Natural parthenogenesis has been observed in many lower animals (it is characteristic of the rotifers), especially insects, e.g.
..... Click the link for more information. , which does not involve fertilization or result in a viable human embryo.) In 2013, however, scientists at Oregon Health and Science Univ. reported that they had created such stem cells using genetic material from human skin cells and donated eggs.
Because extraction of embryonic stem cells destroys the embryo, the use of embryonic stem cells has been opposed by opponents of abortionabortion,
expulsion of the products of conception before the embryo or fetus is viable. Any interruption of human pregnancy prior to the 28th week is known as abortion. The term spontaneous abortion, or miscarriage, is used to signify delivery of a nonviable embryo or fetus due
..... Click the link for more information. . Japanese researchers led by Shinya YamanakaYamanaka, Shinya,
1962–, Japanese physician and researcher, grad. Kobe Univ. (M.D., 1987), Osaka City Univ. (Ph.D., 1993). He was a professor at Osaka City Univ. (1996–99), the Nara Institute of Science and Technology (1999–2005), and the Institute for Frontier
..... Click the link for more information. used retroviruses in 2007 to transfer transcription factors to human skin cells and induce those cells to become stem cells (called induced pluripotent stem cells); Yamanaka's team had previously (2006) achieved similar results with mouse cells. In 2010 an American team announced that they had induced human skin cells to become stem cells using messenger RNA to reprogram the cells. Studies with mice have shown, however, that unlike embryonic stem cells induced stem cells are subject to attack by the recipient's immune system. Treatment with stem cells in humans is experimental and can have unexpected and damaging side-effects; some methods of producing mouse stem cells with retroviruses have led to significant rates of cancer when those cells have been transferred to mice.
The first embryonic stem cells to be isolated were extracted by British researchers from mouse blastocysts; the first human stem cells isolated and cultured were extracted by American scientists in 1998. In 1994 a National Institutes of Health (NIH) panel argued that creating human embryos for use in certain experiments might be justified, but Congress subsequently enacted (1995) a ban on federal financing for research involving human embryos in reaction to that report. The Dept. of Health and Human Services ruled in 1999, however, that that ban did not apply to financing work with stem cells, and guidelines for financing such research were issued by NIH the next year.
President George W. BushBush, George Walker,
1946–, 43d President of the United States (2001–9), b. New Haven, Conn. The eldest son of President George H. W. Bush, he was was raised in Texas and, like his father, attended Phillips Academy in Andover, Mass., and Yale, graduating in 1968.
..... Click the link for more information. , who had campaigned against financing embryonic stem cell research, announced in Aug., 2001, that he would support federal funding of research with embryonic stem cells, but only with the estimated 60 stem cell lines then existing. Some scientists challenged the assumption that these 60 stem cell lines would be sufficient for experimental and therapeutic needs, while others said the figure included some stem cell lines that had not yet been determined to be viable. In fact, in 2004, there were only 15 approved stem cell lines available to researchers funded by the U.S. government. The restrictions did not prevent other researchers, in the United States and elsewhere, from developing new embryonic stem cell lines and undertaking research with them using private funding, and California voted (2004) to create a $3 billion fund to underwrite embryonic stem cell research. A federal legislation that would have expanded the number of stem cell lines available for federally funded research was vetoed by the President Bush in July, 2006. The executive order issued by Bush was overturned in Mar., 2009, by President Barack Obama.
See also fetal tissue implantfetal tissue implant
or fetal cell therapy,
implantation of tissue from a fetus into a patient. In experimental procedures, fetal brain tissue has been implanted in the brains of patients with Parkinson's disease so that the fetal tissue will supply chemicals lacking
..... Click the link for more information. .
Cells that have the ability to self-replicate and give rise to specialized cells. Stem cells can be found at different stages of fetal development and are present in a wide range of adult tissues. Many of the terms used to distinguish stem cells are based on their origins and the cell types of their progeny.
There are three basic types of stem cells. Totipotent stem cells, meaning their potential is total, have the capacity to give rise to every cell type of the body and to form an entire organism. Pluripotent stem cells, such as embryonic stem cells, are capable of generating virtually all cell types of the body but are unable to form a functioning organism. Multipotent stem cells can give rise only to a limited number of cell types. For example, adult stem cells, also called organ- or tissue-specific stem cells, are multipotent stem cells found in specialized organs and tissues after birth. Their primary function is to replenish cells lost from normal turnover or disease in the specific organs and tissues in which they are found.
Totipotent stem cells occur at the earliest stage of embryonic development. The union of sperm and egg creates a single totipotent cell. This cell divides into identical cells in the first hours after fertilization. All these cells have the potential to develop into a fetus when they are placed into the uterus. The first differentiation of totipotent cells forms a hollow sphere of cells called the blastocyst, which has an outer layer of cells and an inner cell mass inside the sphere. The outer layer of cells will form the placenta and other supporting tissues during fetal development, whereas cells of the inner cell mass go on to form all three primary germ layers: ectoderm, mesoderm, and endoderm. The three germ layers are the embryonic source of all types of cells and tissues of the body. Embryonic stem cells are derived from the inner cell mass of the blastocyst. They retain the capacity to give rise to cells of all three germ layers. However, embryonic stem cells cannot form a complete organism because they are unable to generate the entire spectrum of cells and structures required for fetal development. Thus, embryonic stem cells are pluripotent, not totipotent, stem cells.
Embryonic germ (EG) cells differ from embryonic stem cells in the tissue sources from which they are derived, but appear to be similar to embryonic stem cells in their pluripotency. Human embryonic germ cell lines are established from the cultures of the primordial germ cells obtained from the gonadal ridge of late-stage embryos, a specific part that normally develops into the testes or the ovaries. Embryonic germ cells in culture, like cultured embryonic stem cells, form embryoid bodies, which are dense, multilayered cell aggregates consisting of partially differentiated cells. The embryoid body-derived cells have high growth potential. The cell lines generated from cultures of the embryoid body cells can give rise to cells of all three embryonic germ layers, indicating that embryonic germ cells may represent another source of pluripotent stem cells.
Much of the knowledge about embryonic development and stem cells has been accumulated from basic research on mouse embryonic stem cells. Since 1998, however, research teams have succeeded in growing human embryonic stem cells in culture. Human embryonic stem cell lines have been established from the inner cell mass of human blastocysts that were produced through in vitro fertilization procedures. The techniques for growing human embryonic stem cells are similar to those used for growth of mouse embryonic stem cells. However, human embryonic stem cells must be grown on a mouse embryonic fibroblast feeder layer or in media conditioned by mouse embryonic fibroblasts. Human embryonic stem cell lines can be maintained in culture to generate indefinite numbers of identical stem cells for research. As with mouse embryonic stem cells, culture conditions have been designed to direct differentiation into specific cell types (for example, neural and hematopoietic cells).
Adult stem cells occur in mature tissues. Like all stem cells, adult stem cells can self-replicate. Their ability to self-renew can last throughout the lifetime of individual organisms. But unlike embryonic stem cells, it is usually difficult to expand adult stem cells in culture. Adult stem cells reside in specific organs and tissues, but account for a very small number of the cells in tissues. They are responsible for maintaining a stable state of the specialized tissues. To replace lost cells, stem cells typically generate intermediate cells called precursor or progenitor cells, which are no longer capable of self-renewal. However, they continue undergoing cell divisions, coupled with maturation, to yield fully specialized cells. Such stem cells have been identified in many types of adult tissues, including bone marrow, blood, skin, gastrointestinal tract, dental pulp, retina of the eye, skeletal muscle, liver, pancreas, and brain. Adult stem cells are usually designated according to their source and their potential. Adult stem cells are multipotent because their potential is normally limited according to their source and their potential. Adult stem cells are multipotent because their potential is normally limited to one or more lineages of specialized cells. However, a special multipotent stem cell that can be found in bone marrow, called the mesenchymal stem cell, can produce all cell types of bone, cartilage, fat, blood, and connective tissues.
Blood stem cells, or hematopoietic stem cells, are the most studied type of adult stem cells. The concept of hematopoietic stem cells is not new, since it has been long realized that mature blood cells are constantly lost and destroyed. Billions of new blood cells are produced each day to make up the loss. This process of blood cell generation called hematopoiesis, occurs largely in the bone marrow. Another emerging source of blood stem cells is human umbilical cord blood. Similar to bone marrow, umbilical cord blood can be used as a source material of stem cells for transplant therapy. However, because of the limited number of stem cells in umbilical cord blood, most of the procedures are performed for young children of relatively low body weight.
Neural stem cells, the multipotent stem cells that generate nerve cells, are a new focus in stem cell research. Active cellular turnover does not occur in the adult nervous system as it does in renewing tissues such as blood or skin. Because of this observation, it had been a dogma that the adult brain and spinal cord were unable to regenerate new nerve cells. However, since the early 1990s, neural stem cells have been isolated from the adult brain as well as fetal brain tissues. Stem cells in the adult brain are found in the areas called the subventricular zone and the ventricle zone. Another location of brain stem cells occurs in the hippocampus, a special structure of the cerebral cortex related to memory function. Stem cells isolated from these areas are able to divide and to give rise to nerve cells (neurons) and neuron-supporting cell types in culture.
Stem cell plasticity refers to the phenomenon of adult stem cells from one tissue generating the specialized cells of another tissue. The long-standing concept of adult organ-specific stem cells is that they are restricted to producing the cell types of their specific tissues. However, a series of studies have challenged the concept of tissue restriction of adult stem cells. Although the stem cells appear able to cross their tissue-specific boundaries, crossing occurs generally at a low frequency and mostly only under conditions of host organ damage. The finding of stem cell plasticity carries significant implications for potential cell therapy. For example, if differentiation can be redirected, stem cells of abundant source and easy access, such as blood stem cells in bone marrow or umbilical cord blood, could be used to substitute stem cells in tissues that are difficult to isolate, such as heart and nervous system tissue. See Cell differentiation, Embryology, Embryonic differentiation, Germ layers, Hematopoiesis, Regeneration (biology), Transplantation biology