Stem Cells

Picture of the stem cell cycle

Stem cells are cells that have the potential to develop into many different or specialized cell types. Stem cells can be thought of as primitive, "unspecialized" cells that can divide and become specialized cells of the body such as liver cells, muscle cells, blood cells, and other cells with specific functions.

Stem cells are referred to as "undifferentiated" cells because they have not yet committed to a developmental path that will form a specific tissue or organ. The process of changing into a specific cell type is called differentiation. In some areas of the body, stem cells divide regularly to renew and repair the existing tissue. Bone marrow and gastrointestinal tract are examples of areas in which stem cells function to renew and repair tissue.

The best and most readily understood example of a stem cell in humans is that of the fertilized egg or zygote:

• A zygote is a single cell that is formed by the union of a sperm and an ovum. The sperm and the ovum each carry half of the genetic material required to form a new individual.
• Once that single cell or zygote starts dividing, it is known as an embryo. One cell becomes 2, 2 becomes 4, 4 becomes 8, 8 becomes 16, and so on, doubling rapidly until it ultimately grows into an entire sophisticated organism composed of many different kinds of specialized cells.
• That organism, a person, is an immensely complicated structure consisting of many, many, billions of cells with functions as diverse as those of your eyes, your heart, your immune system, the color of your skin, your brain, etc.
• All of the specialized cells that make up these body systems are descendants of the original zygote, a stem cell with the potential to ultimately develop into all kinds of body cells. The cells of a zygote are totipotent, meaning that they can develop into any type of cell in the body.

The process by which stem cells commit to become differentiated, or specialized, cells is complex and involves the regulation of gene expression. Research is underway to further understand the molecular events and controls necessary for stem cells to become specialized cell types.

Stem cells represent an exciting area of medicine due to their potential to regenerate and repair damaged tissue. Some current therapies, such as bone marrow transplantation, already make use of stem cells and their potential for the regeneration of damaged tissues.

Other therapies that are under investigation involve transplanting stem cells into a damaged body part and directing them to grow and differentiate into healthy tissue.

Stem cells are obtained from a number of different sources depending on the type needed and the disease it is meant to treat.

The most common sources of stem cells include the following:

• Embryonic stem cells
• Fetal stem cells
• Adult stem cells
• Peripheral stem cells
• Perinatal stem cells
• Induced pluripotent stem cells

Embryonic stem cells

During the early stages of embryonic development, cells remain relatively undifferentiated (immature) and appear to possess the ability to become, or differentiate, into almost any tissue within the body. For example, cells taken from one section of an embryo that might have become part of the eye can be transferred into another section of the embryo and could develop into blood, muscle, nerve, or liver cells.

Cells in the early embryonic stage are totipotent (see above) and can differentiate to become any type of body cell. After about 7 days, the zygote forms a structure known as a blastocyst, which contains a mass of cells that eventually become the fetus, as well as trophoblastic tissue that eventually becomes the placenta. If cells are taken from the blastocyst at this stage, they are known as pluripotent, meaning that they can become many different types of human cells. Cells at this stage are often referred to as blastocyst embryonic stem cells. When any type of embryonic stem cells is grown in culture in the laboratory, they can divide and grow indefinitely. These cells are then known as embryonic stem cell lines.

Fetal stem cells

The embryo is referred to as a fetus after the eighth week of development. The fetus contains stem cells that are pluripotent and eventually develop into the different body tissues in the fetus.

Adult stem cells

Adult stem cells are present in all humans in small numbers. The adult stem cell is one of the classes of cells that we have been able to manipulate quite effectively in the bone marrow transplant arena over the past 30 years. These are stem cells that are largely tissue-specific in their location. Rather than typically giving rise to all of the cells of the body, these cells are capable of giving rise only to a few types of cells that develop into a specific tissue or organ. They are therefore known as multipotent stem cells. Adult stem cells are sometimes referred to as somatic stem cells.

The best example of an adult stem cell is the blood stem cell (hematopoietic stem cell). When we refer to a bone marrow transplant, a stem cell transplant, or a blood transplant, the cell being transplanted is the hematopoietic stem cell or blood stem cell. This cell is a very rare cell that is found primarily within the bone marrow of an adult.

One of the exciting discoveries of the last years has been the overturning of a long-held scientific belief that an adult stem cell was a completely committed stem cell. It was previously believed that a hematopoietic, or blood-forming stem cell, could only create other blood cells and could never become another type of stem cell. There is now evidence that some of these committed adult stem cells can change direction to become a stem cells in a different organ.

For example, there are some models of bone marrow transplantation in rats with damaged livers in which the liver partially re-grows with cells that are derived from transplanted bone marrow. The use of stem cells to repair damaged tissues is part of a field known as regenerative medicine. Similar studies can be done showing that many different cell types can be derived from each other. It appears that heart cells can be grown from bone marrow stem cells, that bone marrow cells can be grown from stem cells derived from muscle, and that brain stem cells can turn into many types of cells.

Peripheral blood stem cells 

Most blood stem cells are present in the bone marrow, but a few are present in the bloodstream. This means that these so-called peripheral blood stem cells (PBSCs) can be isolated from a drawn blood sample. The blood stem cell is capable of giving rise to a very large number of very different cells that make up the blood and immune system, including red blood cells, platelets, granulocytes, and lymphocytes.

• Red blood cells carry oxygen around the body and give the blood its color.
• Platelets are cell fragments that stop a person from bleeding and help the body to clot and heal when it is cut.
• Granulocytes are a type of white blood cell that helps fight the bacterial infection.
• Lymphocytes are a type of white blood cell that is part of the immune system, helps fight other infections, and also may be involved in protection against cancer.

All of these very different cells with very different functions are derived from a common, ancestral, committed blood-forming (hematopoietic), a stem cell.

Perinatal stem cells

Blood from the umbilical cord and the amniotic fluid contains some stem cells that are genetically identical to the newborn. Like adult stem cells, these are multipotent stem cells that can differentiate into certain, but not all, cell types. For this reason, umbilical cord blood is often banked, or stored, for possible future use should the individual require stem cell therapy.

Induced pluripotent stem cells 

Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically converted to an embryonic stem cell-like state. Human iPSCs can differentiate and become multiple different fetal cell types. iPSCs are valuable aids in the study of disease development and drug treatment, and they may have future uses in transplantation medicine. Further research is ongoing regarding the development and use of these cells.

Embryonic stem cells and embryonic stem cell lines have received much public attention concerning the ethics of their use or non-use. Clearly, there is hope that a large number of treatment advances could occur as a result of growing and differentiating these embryonic stem cells in the laboratory. It is equally clear that each embryonic stem cell line has been derived from a human embryo created through in-vitro fertilization (IVF) or through cloning technologies, with all the attendant ethical, religious, and philosophical problems, depending upon one's perspective.

Routine use of stem cells in therapy has been limited to blood-forming stem cells (hematopoietic stem cells) derived from bone marrow, peripheral blood, or umbilical cord blood. Bone marrow transplantation is the most familiar form of stem cell therapy and the only instance of stem cell therapy in common use. It is used to treat cancers of the blood cells (leukemias) and other disorders of the blood and bone marrow.

In bone marrow transplantation, the patient's existing white blood cells and bone marrow are destroyed using chemotherapy and radiation therapy. Then, a sample of bone marrow (containing stem cells) from a healthy, immunologically matched donor is injected into the patient. The transplanted stem cells populate the recipient's bone marrow and begin producing new, healthy blood cells.

Umbilical cord blood stem cells and peripheral blood stem cells can also be used instead of bone marrow samples to repopulate the bone marrow in the process of bone marrow transplantation.

The U.S. Food and Drug Administration (FDA) has approved several stem cell therapies for certain medical conditions. However, many stem cell therapies are still in the experimental phase and have not been fully tested. Despite the marketing of unproven stem cell therapies, the FDA has taken action against the clinics offering these unapproved therapies.

One common stem cell therapy approved by the FDA includes hematopoietic stem cell transplantation (HSCT), which requires transplanting stem cells to treat diseases that occur in the bone marrow and blood.

Stem cell therapy is an exciting and active field of biomedical research. Scientists and physicians are investigating the use of stem cells in therapies to treat a wide variety of diseases and injuries. For stem cell therapy to be successful, several factors must be considered. The appropriate type of stem cell must be chosen, and the stem cells must be matched to the recipient so that they are not destroyed by the recipient's immune system. It is also critical to develop a system for the effective delivery of stem cells to the desired location in the body. Finally, devising methods to "switch on" and control the differentiation of stem cells and ensure that they develop into the desired tissue type is critical for the success of any stem cell therapy.

Researchers are currently examining the use of stem cells to regenerate damaged or diseased tissue in many conditions, including:

• Heart disease
• Parkinson's disease
• Spinal cord injury
• Diabetes mellitus
• Amyotrophic lateral sclerosis
• Arthritis
• Burns