Stem Cells

Every tissue and organ in the human body is made up of different types of cells. Cells that make up skin, for example, are different from those that make up the heart. This makes it impossible for cells that make up one tissue or organ to be transferred to another tissue or organ.

However, all cells share one thing in common - they come from one cell source. In the early stages of human development, these cells can become any tissue or organ - that is, they have not yet become specialized. These cells are called stem cells.

Stem cells have two important characteristics that make them different from other types of cells. First, as noted above, all stem cells are unspecialized, and renew themselves for long periods of time through cell division. Second, under certain biochemical cues they can be made to differentiate (see below). This means that they can divide into cells with special functions, such as the beating cells of the heart muscle or the insulin-producing cells of the pancreas.

Types of stem cells

Stem cells come in three forms: embryonic stem (ES) cells, embryonic germ cells, and adult stem cells. ES cells come from embryos; embryonic germ cells come from testes, and adult stem cells can come from bone marrow. Scientists work mostly with ES cells and adult stem cells.

ES cells are found in the early beginnings of human life - at the blastocyst stage of human development. This stage is from four to five days after the union of the sperm and the egg, before the embryo implants in the uterus. The 20 or so stem cells in the blastocyst are called pluripotent, which means they are capable of forming all embryonic tissues, but they cannot form a complete organism without support from the placenta.

ES cells come from embryos, fetuses and some can come from the blood of the umbilical cord after birth.

Differentiation

The process by which the stem cell can become a specific cell type is called differentiation. Stem cell differentiation begins when they are exposed to certain biochemical cues - either physiological or experimental. Biochemical cues in different parts of the body stimulate stem cells to grow into the specific cells needed in that location.

All stem cells have the capacity to differentiate, but to different degrees.

• Totipotent stem cells can become any cell in the human body;
• Pluripotent stem cells can become almost any cell in the human body, but they cannot become placental tissue needed for development in the human uterus; and
• Multipotent stem cells can become only a certain type of cell, such as a blood cell.

Adult stem cells are found in the fetus, child and adult. These "adult" stem cells are found in many human tissues, such as blood, brain, intestine, skin and muscle. They are responsible for the repair and regeneration in the body.

It was long thought that adult stem cells had less flexibility than ES cells, and that they could normally form only cell types the same as the tissue of origin. However, recent discoveries are pointing to new sources of stem cells within the adult body. Research into adult stem cells has the potential to eliminate ethical concerns about experimentation or transplantation of ES cells. The use of adult stem cells would also reduce the chance of transplant rejection because patients could receive transplants of their own stem cells.

The possibility that adult stem cells also have a greater "plasticity" than previously believed has resulted in new experimentation. For example, scientists now believe that certain types of adult stem cells can develop into cells of another tissue (for example human blood stem cells have been shown to differentiate into liver cells if the conditions are right). However, no adult stem cell has been definitively shown to be completely pluripotent.

Some scientists are now calling adult stem cells "somatic stem cells". Unlike ES cells, which are defined by where they originated (in the inner cell mass of the blastocyst), the origin of adult stem cells in mature tissues is unknown.

Some current research

Research into adult stem cells has caused a lot of excitement. Because adult stem cells have been found in many more tissues than originally thought possible, scientists have asked whether adult stem cells could be used for transplants. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of therapies for many serious common diseases.

Some diseases have already been targeted. For example, adult blood stem cells have been used to treat hematologic (blood) cancers. Adult blood-forming stem cells from bone marrow have been used in transplants for over 30 years. The stem cells of the matched donor are purified, and the patient's bone marrow is then destroyed by radiation and reconstituted with the stem cell graft.

Several groups have been working on animal models in which pluripotent stem cells are grafted into damaged hearts. The stem cells were shown to "beat" with the surrounding heart cells. Several animal and early human trials are also underway to use pluripotent or adult stem cells to repair damage to the nervous system, such as in spinal cord injury, Parkinson's disease and Alzheimer's disease.

While large numbers of ES cells can be grown in a laboratory, adult stem cells are rare in mature tissues and a way to increase their numbers in cell culture has not yet been developed. Much research is ongoing in this area, as large numbers of cells are needed for stem cell replacement therapies.

Potential applications of human stem cells

One of the goals of scientists is to control cell differentiation. This would allow them to create any tissue or organ in the body from a single stem cell. This research involves many biotechnology applications, such as the study of stem cell genetics, biological factors (normally occurring proteins that the body needs to function normally), receptors on the stem cells and stem cell physiology. Researchers are encouraging adult stem cells, such as those from the skin, to become other types of tissue, such as nerve or muscle. Of all the adult stem cells identified so far, hematopoeitic stem cells (a stem cell from which all red and white blood cells develop) have been the most studied.

Scientists are using genetic modification to expand the potential therapeutic applications of stem cells. Stem cells can be modified to produce enzymes or factors, such as insulin, before being transplanted into the body. Stem cells can also be modified to resist certain infections. For example, studies are underway to create stem cells resistant to HIV. Once implanted, these stem cells would repopulate the diseased immune system of AIDS patients with cells resistant to the disease.

However, the main application of stem cells is still to replace damaged, diseased or dead cells. Once implanted, a stem cell can differentiate into the correct cell type, and form natural connections with the surrounding tissue, which is very important in neurodegenerative diseases such as Parkinson's and Alzheimer's.

Stem cells may also be useful in tissue-engineering applications, such as the production of complete organs, including heart, liver, kidneys, eyes or even parts of the brain.

Stem cells represent a potentially unlimited source of experimental tissue, which would permit research into other areas. For example, researchers could test stem cells derived from culture in the laboratory for the effects of known environmental hazards and genetic mutations on the relevant human tissue. This would provide more applicable information than that obtained in animal models.