Stem Cells and Cord Blood

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.

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Umbilical Cord Blood

Following the birth of a baby, the umbilical cord usually is discarded along with the placenta. However, it is now known that blood retrieved from the umbilical cord is a rich source of stem cells. Stem cells are unspecialized blood cells that produce all other blood cells, including blood-clotting platelets and red and white blood cells. Like donated bone marrow, umbilical cord blood can be used to treat various genetic disorders that affect the blood and immune system, leukemia and certain cancers, and some inherited disorders of body chemistry. To date, more than 45 disorders can be treated with stem cells from umbilical cord blood.

Currently, commercial companies provide services to parents to store their newborn baby’s cord blood. Prospective parents who are considering this option should have as much information as possible to make an informed decision.

What are stem cells and why are they valuable?

Blood stem cells, most often found deep in bone marrow, are the factory of the blood system. They continually make new copies of themselves and produce cells that make every other type of blood cell. Stem cells are the key to successful bone marrow transplantations (BMTs) because they continue to manufacture blood cells indefinitely.

Bone marrow transplants can be lifesaving for people with leukemia (cancer of the white blood cells) and other cancers, or for those with serious blood disorders, such as aplastic anemia, in which the body does not produce enough blood cells. Stem cells can help enhance a person’s blood producing capability and immune system that are impaired through an inherited (genetic) defect or that have been severely damaged or deliberately destroyed by cancer treatments. At present, donated bone marrow is the most common source of stem cells.

What are the advantages of stem cells from cord blood?

Studies suggest that stem cells from cord blood offer some important advantages over those retrieved from bone marrow. For one thing, stem cells from cord blood are much easier to get because they are readily obtained from the placenta at the time of delivery. Harvesting stem cells from bone marrow requires a surgical procedure, usually under general anesthesia, that can cause post-operative pain and poses a small risk to the donor.

A broader range of recipients may benefit from cord blood stem cells. These can be stored and transplanted back into the donor, to a family member or to an unrelated recipient. For a bone marrow transplant to succeed, there must be a nearly perfect match of certain tissue proteins between the donor and the recipient. When stem cells from cord blood are used, the donor cells appear more likely to “take” or engraft, even when there are partial tissue mismatches.

A potentially fatal complication called graft versus host disease (GVHD), in which donor cells can attack the recipient’s tissues, appears to occur less frequently with cord blood than with bone marrow. This may be because cord blood has a muted immune system and certain cells, usually active in an immune reaction, are not yet educated to attack the recipient. A 2000 study found that children who received a cord blood transplant from a closely matched sibling were 59 percent less likely to develop GVHD than children who received a bone marrow transplant from a closely matched sibling.

The use of cord blood may make blood stem cell transplants available more quickly for people who need them. About 30,000 individuals each year are diagnosed with conditions that could be treated with a bone marrow transplant. Approximately 25 percent of these individuals have a relative who is an appropriate tissue match. While suitable donors can be located for many through national bone marrow registries, the process can take months. Donors can be located within 4 months for about 50 percent of patients. It often is more difficult to find a bone marrow match for members of non-white ethnic and racial groups; transplants from cord blood may make timely treatment available for more of these individuals. Banked stem cells from cord blood can be more readily available, and this can be especially crucial for patients with severe cases of leukemia, anemia or immune deficiency who would, otherwise, die before a match can be found.

Cord blood also is less likely to contain certain infectious agents, like some viruses, that can pose a risk to transplant recipients.

In addition, some studies suggest that cord blood may have a greater ability to generate new blood cells than bone marrow. Ounce for ounce, there are nearly 10 times as many blood-producing cells in cord blood. This fact suggests that a smaller number of cord blood cells are needed for a successful transplantation.

In addition, cord blood stem cells offer some exciting possibilities for gene therapy for certain genetic diseases, especially those involving the immune system. Donald Kohn, MD, and colleagues at the Children’s Hospital of the University of Southern California in Los Angeles and the University of California in San Francisco, made the first attempt at gene therapy with cord blood in 1993 in three children suffering from adenosine deaminase (ADA) deficiency, a potentially fatal defect that cripples the immune system. The children, who also receive additional drug treatment, appear healthy to date, even though their blood now carries only a small amount of the gene introduced into their stem cells.

Source: http://www.marchofdimes.com/professionals/681_1160.asp