Multipotent stem cells
Related Terms
Adult stem cells, blastocysts, cell culture, differentiation, embryo, embryonic stem cells, ES cells, in vitro, inner cell mass, multipotent, multipotent stem cells, potency, proliferation, pluripotent, pluripotent stem cells, totipotent, totipotent stem cells, umbilical cord stem cells, unipotent, unipotent stem cells.
Background
Differentiated cells are specialized for a particular function and do not have the ability to generate other kinds of cells or to go back to being undifferentiated, or unspecialized. Some examples of differentiated cells are heart muscle cells, nerve cells, and blood cells. Differentiated cells can grow for only so long before they die off to make room for newly differentiated cells that will replace them and perform the same function.
Stem cells, on the other hand, are undifferentiated cells and do not perform a certain function within the body. Stem cells have the ability to self-renew while maintaining an unspecialized state. In other words, stem cells can remain as stem cells and do not need to differentiate into another type of cell in order to grow and survive. However, they also have the ability to develop into differentiated cells such as nerve cells, muscle cells, or blood cells.
They can proliferate, or self-renew, indefinitely. Adult stem cells are able to develop only into the tissue or organ from which they originally developed. These stem cells can act as a repair system for the body, replenishing specialized cells, but can also maintain the normal cellular turnover of regenerative organs, such as blood, skin, or intestinal tissues.
By studying stem cells scientists may better understand the process of embryonic development. Furthermore, stem cell research may reveal how healthy cells replace damaged cells in adult organisms.
One important area of stem cell research includes understanding how a stem cell can remain undifferentiated until a specific type of cell is needed for tissue repair and what internal and external signals are involved in getting a stem cell to proliferate. Internal signals may be coded by genes, which are contained in the cell's chromosomes. External signals include molecules secreted by other cells and within the cell's environment, and by physical contact with other cells.
Stem cells can be grown in vitro, meaning they can be grown in a laboratory, thereby providing a controlled environment without any known factors that may influence their growth.
Through stem cell research, scientists hope to develop cell-based therapies to treat certain conditions. Such therapies, also known as regenerative or reparative medicine, are being studied for use in several diseases, including Parkinson's disease, Alzheimer's disease, osteoarthritis, rheumatoid arthritis, diabetes, spinal cord injuries, stroke, and heart disease.
Methods
Embryonic stem cells: Human embryonic stem (ES) cells used in stem cell research are derived from embryos grown in an in vitro fertilization clinic and donated for research purposes. They are not grown in a woman's body.
Embryonic cells may be grown, or cultured, in a laboratory for research purposes. In stem cell research, the inner cell mass, which is the source of ES cells, is placed in a culture dish containing a nutrient broth known as culture medium. Here, the cells divide and spread over the surface of the dish.
When the stem cells begin to fill the plate, they are divided among several new plates to prevent overcrowding. It is also important at this stage to keep the stem cells undifferentiated. This process, called subculturing, may be repeated for several months and may generate millions of embryonic stem cells. These can be frozen and stored in liquid nitrogen for an indeterminate period of time; there is evidence that stem cells have been viable after being frozen for up to 15 years. Frozen cells may also be shipped to other laboratories, where they may be used for further cultures and experimentation.
When stem cells are maintained in the laboratory, they are routinely tested for traits that are specific to undifferentiated stem cells. This is necessary to make sure that the stem cells have not begun to differentiate into specific cell types.
To generate cultures of specific types of specialized or differentiated cells, scientists try to control the environment in which the stem cells grow. This may include changing the culture medium, altering the growing conditions, or inserting specific genes. The process of producing specific cells from stem cell cultures is known as directed differentiation and is conducted with multipotent cells.
Directed differentiation may allow scientists to use stem cell research to treat Parkinson's disease, diabetes, traumatic spinal cord injury, Purkinje cell degeneration (a type of cell in the brain located in the cerebellum that is responsible for all motor output from the brain), Duchenne's muscular dystrophy, heart disease, and loss of vision and hearing.
Adult stem cells: Adult stem cells are undifferentiated or non-specialized cells, found in adult tissues. They tend to grow into cell types from the tissue in which they are located for the purpose of repairing tissue damage and maintaining normal cell renewal. Adult stem cells located in the bone marrow, for example, might develop into any one of the several types of blood cells. If removed from their location and placed elsewhere, however, it is possible for adult stem cells to develop into different types of cells. This quality is called plasticity.
Research using adult stem cells is a growing area of interest. If adult stem cells can be used in transplantation and the differentiation process can be controlled, these cells may become the foundation of many disease therapies.
Adult stem cell research focuses on the use of hematopoietic stem cells, which form all the types of blood cells in the body, and bone marrow stromal cells, which form bone, cartilage, fat, and fibrous connective tissues. Tissues that contain adult stem cells include the bone marrow, blood, blood vessels, skeletal muscle, skin, and liver. In addition, the adult brain contains stem cells that can be used to generate nerve cells.
Additional research uses epithelial stem cells, which are located in the lining of the digestive tract to generate absorptive cells, goblet cells, Paneth cells, and enteroendocrine cells, which are all located in the intestine. Skin stem cells, which are located in the basal layer of the skin and at the base of hair follicles, can generate keratinocytes, hair follicle cells, and skin cells.
Adult stem cells are currently the only type of stem cell used to treat human disease. Hematopoietic stem cells found in the bone marrow have been used in bone marrow transplants for more than 40 years. Other uses of these cells include leukemia, lymphoma, and several inherited blood disorders. Early research suggests that adult stem cells may be useful in the treatment of diabetes, advanced kidney cancer, Parkinson's disease, multiple sclerosis, Huntington's disease, Alzheimer's disease, and spinal cord injuries, among others.
There are several differences between embryonic and adult stem cells. While embryonic stem cells can be generated indefinitely, there is a limited amount of adult stem cells. While embryonic stem cells may develop into any cell type, adult stem cells are more specific. Adult stem cells may offer patient-specific advantages, such as a low risk of tissue or organ rejection.
Research
Stem cell research may have numerous applications.
Replace damaged tissue: Stem cell research has the potential to be used in cell-based therapies, which treat patients by transplanting specialized cells. Stem cells found in the bone marrow, for example, may be transplanted into patients with leukemia to generate new blood cells. New research has shown that human bone marrow stem cells may be used to regenerate liver cells, and scientists hope that stem cells will be able to repair the spinal cord following injury.
Aging: The process of aging results from cells lacking the ability to repair themselves. Stem cells could potentially be used in what is being called restorative medicine, which aims to produce therapies that can extend an individual's lifespan.
Cancer: Although research has shown that cancer stem cells are rare, the presence of just once cancer stem cell is sufficient to initiate and maintain a malignant tumor. It is important that researchers learn how a stem cell can give rise to a malignant tumor; this may help find a cure for cancer.
Disease and injury: Stems cells can be used to replace cells that have been damaged or lost during the course of an injury or disease. Therefore, stem cells are being investigated as a treatment for various diseases, including diabetes, advanced kidney cancer, Parkinson's disease, multiple sclerosis, Huntington's disease, Alzheimer's disease, and spinal cord injuries.
New drug testing: Current testing of new drugs is conducted using laboratory animals, such as rats. Research has shown that a drug that is not toxic in a rat may very well be toxic in a human; therefore, these methods can be unreliable. Before testing new drugs or chemicals in human trials, they can be tested on stem cells. In the laboratory, stem cells could be manipulated to grow into specific types of cells (for example, cancer cells) in order to test the effect of a certain compound (for example, a new cancer drug). This may offer safer, cheaper, and more acceptable testing alternatives.
Testing gene therapy: Gene therapy is the process by which genes are inserted into an individual's cells with the goal of treating or preventing a disease. Research has shown that it is possible for bone marrow stem cells to differentiate into other kinds of cells, such as cells that line lung tissue. It is also possible for scientists to change a defective gene in these cells so that once they are introduced into the body they no longer express the defective gene. This research has been conducted in patients with cystic fibrosis, a disease characterized by a certain genetic mutation.
Implications
The use of stem cells in research is intensely debated, largely due to the ethical concerns regarding the use of embryonic stem (ES) cells. Many groups oppose ES cell research because human embryos are sacrificed to produce ES cell lines.
In addition, pro-life activists argue that all human embryos have the right to live, regardless of why they are created.
Proponents of ES cell research argue that, with consent, excess embryos from in vitro fertilization procedures should be made available research purposes. Some believe that the outcomes may bring dramatic improvements to the field of medicine.
The use of a single-cell biopsy, which allows for a single cell to be removed from an embryo 2-3 days after in vitro fertilization, would allow scientists to generate embryonic stem cells without embryonic destruction. Stem cells can also be obtained in other ways that do not require the destruction of an embryo, such as through the umbilical cord and from human bone marrow.
In response to this debate, the National Institutes of Health's Department of Clinical Bioethics offers additional resources about the ethics of stem cell research.
Limitations
The use of stem cells in research is intensely debated, largely due to the ethical concerns regarding the use of embryonic stem (ES) cells. Many groups oppose ES cell research because human embryos are sacrificed to produce ES cell lines.
In 2001, President George W. Bush approved federal funding for research of more than 60 pre-existing stem cell lines that have already been isolated from embryos. The embryos from which the existing stem cell lines were created had already been destroyed.
Federal funds are not available to isolate stem cells from additional embryos that have been fertilized in a laboratory and then donated for research purposes. Because the government does not currently support using embryos for research, it may only be conducted with private funds.
Future research
Stem cell research may have the potential to help scientists understand how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research may also make possible cell-based therapies to treat disease, to test drugs, and to understand birth defects. Areas of potential use for stem cells include Parkinson's disease, Alzheimer's disease, osteoarthritis, rheumatoid arthritis, diabetes, spinal cord injuries, stroke, and heart disease.
Ongoing research is focused on identifying different types of adult stem cells, and in which tissues they exist. Scientists are also studying the extent of adult stem cell plasticity, which refers to their ability to develop into various types of specialized cells; the extent to which adult stem cells can be manipulated; and what the signals are that determine proliferation and differentiation of adult stem cells.
Future research will most likely examine the usefulness of stem cells in gene therapies. This would allow scientists to change a defective gene in an individual's stem cells and then allow these cells to differentiate into a particular cell with a restored gene. This may help in recovery from a variety of diseases with a genetic basis.
Author information
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
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Types of stem cells
First identified in 1998, stem cells are found in blastocysts, which are the structures found in the early growth stages of an embryo, prior to implantation on the uterine wall. The function of stem cells in an embryo is to differentiate into specialized tissues within the embryo to form the heart, lungs, brain, and other organs and tissues.
Stem cells are often classified by the tissues from which they are derived. They may also be classified by their potency, which refers to the potential of a stem cell to self-renew and differentiate into different types of tissues.
Totipotent stem cells: Totipotent stem cells are produced from the fusion of an egg and a sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.
Pluripotent stem cells: Pluripotent stem cells are the descendants of totipotent cells and can become any type of cell. These are different from totipotent cells because they can self-renew.
Multipotent stem cells: Multipotent stem cells can produce cells of only a closely related family of cells. For example, hematopoietic stem cells differentiate into red blood cells, white blood cells, and platelets.
Unipotent stem cells: Unipotent stem cells can produce only one cell type, but have the property of self-renewal, which distinguishes them from non-stem cells.
Embryonic stem cells: Embryonic stem (ES) cells are the pluripotent descendants of totipotent stem cells and can become any type of cell. ES cells are derived from the blastocyst. After the blastocyst implants into the wall of the uterus, it further develops into the embryo and its surrounding tissues, such as the placenta and the amniotic sac.
Human ES cells were first isolated in 1998 and are used in stem cell research. These cells were derived from blastocysts grown in an in vitro fertilization clinic, rather than inside a woman's body. With consent from the family, they were then donated by the clinic for research purposes. During in vitro fertilization, it is typical for a number of egg cells to become fertilized and for only a proportion of those fertilized cells to be implanted into a woman's uterus. Therefore, upon consent of the family, the embryos that are not implanted may be donated for research purposes.
On August 9, 2001, the President of the United States announced that federal funds may be used for research using embryonic stem cells if certain criteria are met. These criteria include that the stem cells were obtained prior to 9:00 p.m. Eastern Time on August 9, 2001; that the stem cells were obtained from an embryo that was created for reproductive purposes and no longer needed; that informed consent was obtained for the donation of the embryo; and that the donation did not result in financial gain to any involved party.
Umbilical cord stem cells: The umbilical cord, which connects an embryo or fetus to the placenta while in the womb, is another source of stem cells. Some parents are electing to save the blood from their child's umbilical cord so that it is available in the event that a family member develops a disease in which stem cells could be useful, such as a bone marrow transplant to treat leukemia. Similar to embryonic stem cells, umbilical cord stem cells are pluripotent and can develop into any type of cell.
Adult stem cells: Many different types of stem cells are found in adult tissues. They are unlike embryonic stem cells in that they can only grow into cell types of the tissue where they are located, and they are involved in tissue repair and in helping to maintain normal cell renewal. For example, bone marrow stem cells are found in the bone marrow and can develop into any one of the several types of blood cells. It was thought that all adult stem cells were multipotent, in that they could produce only cells of a closely related family of cells. However, research has shown the potential of bone marrow stem cells to differentiate into functioning liver cells.