About Stem Cells

Stem cells play a central role in the normal growth and development of animals and humans. Normal growth and development, including the maintenance of tissues and organs in the body, require the production of new cells via cell division. However, specialised cells, such as blood and muscle cells, are unable to divide and produce copies of themselves. Instead they are replenished from populations of stem cells, which have the unique ability to divide to produce both copies of themselves and other cell types. Stem cells, therefore, play a crucial role in supporting tissues such as blood, skin, and gut that undergo continuous turnover (cell replacement), and muscle, which can be built up according to the body's needs and often damaged during physical exertion.

                                   Stem cells growing in a petri dish.

Why are stem cells interesting?

Stem cells have three properties that distinguish them from other types of cells in the body and make them interesting to scientists:

1. Stem cells are unspecialised

Unlike a red blood cell, which carries oxygen through the blood stream, or a muscle cell that works with other cells to produce movement, a stem cell does not have any specialised physiological properties.

2. Stem cells are able to divide and produce copies of themselves

Stem cells can divide and produce identical copies of themselves, over and over again. This process is called self-renewal and continues throughout the life of the organism. In contrast, specialised cells such as blood and muscle do not normally replicate themselves, which means that when they are seriously damaged by disease or injury, they cannot replace themselves.

3. Stem cells have the potential to produce other cell types in the body

In addition to self-renewal, stem cells can also divide and produce cells that have the potential to become other more specialised cell types, such as blood and muscle cells. This process is called differentiation.
Stem cells from different tissues, and from different stages of development, vary in the number and types of cells that they can give rise to. According to the classical view, as an organism develops the potential of a stem cell to produce any cell type in the body is gradually restricted.

Pluripotent stem cells

Pluripotent stem cells have the potential to develop into any of the cell types of the adult organism. In general, stem cells found during the very early stages of development are pluripotent.

Multipotent stem cells

Multipotent stem cells have the potential to make only a limited range of cell types in the body. In general, stem cells found in the adult body are multipotent.

A stem cell is an unspecialised cell type. When it divides it can either produce identical daughter cells (self-renewal) or it can produce more specialised cell types (differentiation). A central goal in stem cell research is to understand how this choice between self-renewal and differentiation is determined.

Stem Cell Research

Scientists are excited about the potential uses of stem cells in many different areas of research.

Stem cells provide an ideal model for studying the development of organisms

Stem cells may help us understand how a complex organism develops from a fertilised egg. Identifying the factors that determine whether a stem cell chooses to carry on replicating or differentiates into a specialised cell type, will help scientists understand what controls normal cell development.

Stem cells have the ability to replace damaged cells in the body that would otherwise not be replenished

Stem cells have the ability to replace damaged cells in the body. This property has led scientists to investigate the possible use of stem cells in regenerative medicine. Under certain conditions, stem cells can be induced to become other types of cell, such as blood cells and muscle cells, nerve cells, heart cells, or insulin-producing cells. Stem cells may, therefore, hold the key to replacing cells lost in many devastating diseases for which there are currently no cures, for example Parkinson's, heart disease, and diabetes. This potential benefit is responsible for the huge amount of interest in stem cell research.

Stem cells may aid drug discovery

The potential to produce large numbers of specific cell types from human embryonic stem cells also has huge implications for drug discovery. If scientists are able to grow huge amounts of cells that are all the same then pharmaceutical companies could use them to test drugs. The initial stages of testing the effect and toxicity of drugs on cells could easily be investigated and the amount of testing done in animal models significantly reduced.

Stem cells are found in the early embryo, the foetus, the placenta and umbilical cord, and in many tissues of the body. Stem cells isolated from these different tissues, and from different stages of development, vary in the number and types of cells that they can give rise to. In theory, stem cells derived from early embryos have the greatest potential to develop into all cell types. Scientists have focused their research on stem cells derived from developing embryos and adult tissues.

Embryonic Stem Cells

Stem cells can be derived from mammalian embryos, during the very early stages of development. In particular, Embryonic Stem (ES) cells are isolated from embryos that are 5-6 days old. At this early stage the embryo is a ball of cells the size of a pinhead, called a blastocyst. See below for a legal summary.

                                        The human blastocyst

ES cells are derived from a small group of pluripotent cells within the blastocyst, called the inner cell mass. The inner cell mass gives rise to all the highly specialised cells needed to produce an adult organism. This means that ES cells have the potential to make all cell types in the body . 

              Fig.4 ES cells have the potential to make all cell types in the body.

Tissue Stem Cells

Stem cells can be derived from various tissues in adults. To date, stem cells have been found in bone marrow, blood, skin, muscle, liver, brain, the cornea and retina of the eye, the lining of the gastrointestinal tract, and pancreas. The primary role of these stem cells is to maintain, and in some cases repair, the tissue in which they are found. For example, Stem cells that are found in the skin will give rise to new skin cells, ensuring that old/damaged skin cells are replenished. Most research has been done on haematopoietic (blood forming) stem cells isolated from bone marrow and blood.

Stem cells usually only produce cells specific to the tissue in which they are found. Stem cells found in muscle, for example, will normally only give rise to muscle cells. Although adult stem cells are relatively unspecialised, they are nonetheless predetermined to give rise to specific cell types when they differentiate. This means that Tissue stem cells only have the potential to make a limited range of cell types in the body.

If ES cells and adult stem cells are different, which type of stem cell should we use for future research?

• Embryonic stem cells have huge therapeutic potential because they can give rise to every cell type in the body. Adult stem cells, on the other hand, can only give rise to a limited range of cell types.

• Due to the obvious ethical issues surrounding the use of embryonic stem cells for research purposes, strict guidelines and legislation have been established in the UK (see The Law). For some people the origin of ES cells will always be a sensitive issue, therefore adult stem cells could provide an acceptable alternative.

• Until recently, it was thought that adult stem cells could only give rise to the cell types from which they originated. Scientists are now investigating the possibility that an adult stem cell f rom one tissue may, under the right conditions, give rise to cell types of another tissue. For example, it has been reported that stem cells isolated from blood can be induced to differentiate into neural cells. This is a phenomenon called plasticity.

• The ability of adult stem cells to exhibit plasticity increases their therapeutic potential considerably. Unfortunately, new research suggests an alternative explanation for this newly observed phenomenon. In a recently published paper, researchers from ISCR show that the adult stem cells are actually fusing with ES cells in the same culture before differentiating into another cell type. This suggests that the involvement of ES cells is responsible for the unrestricted differentiation.

Most scientists are agreed that it is important to continue to pursue research into both ES cells and tissue stem cells.

Stem cells have the ability to replace damaged cells in the body that would otherwise not be replenished.

This property has led scientists to investigate the possible use of stem cells in regenerative medicine. In particular, scientists are very excited about the potential use of stem cells in the treatment of diseases, such as Parkinson's, heart disease, and diabetes, for which there are currently no cures.

It is hoped that by transplanting the appropriate stem cells into the damaged or diseased tissue of an individual, the transplanted stem cells will regenerate the various cell types of that tissue. Bone marrow transplants and skin grafting are established examples of regenerative medicine. During a bone marrow transplant, for example, haematopoietic stem cells are removed from the bone marrow and transplanted into the patient to generate new blood cells.

Scientists hope to grow stem cells in the laboratory and direct them to produce specialised cell types wanted for transplants or drug screening.

It is hoped that researchers will be able to accurately direct stem cells in the laboratory to produce the specialised cell types wanted for transplantation. A lot of research at the moment is therefore focused on identifying which factors consistently induce stem cells to become certain cell types.

Stem cell therapies, like other tissue transplants, face the problem of being rejected by the patients' immune system. The immune system protects the body against disease by recognising microorganisms that are not its own and destroying them. The immune system also rejects human cells and tissues that do not belong to the body. This has resulted in the failure of many organ transplants, and is an obstacle that must be overcome if stem cell therapies are to succeed.

In particular, stem cell-based therapies that have originated from ES cells will not be recognised by the patients' body and the immune system will try to reject them. Immunosuppressant drugs could be used to repress the immune system and increase the chance that stem cell transplants are accepted by the body. Alternatively, using the patients own cells and tissues will overcome the issue of immune rejection. Stem cell therapies generated by a patient's own stem cells will be recognised by their immune system when transplanted back into the body and so will not be rejected. It is, therefore, very important to continue to pursue research into both ES cells and tissue stem cells.

It is hoped that using the patient's own cells and tissues will overcome the issue of immune rejection.

It is not yet known how transplanted stem cells will behave inside the body. In particular, the potential of ES cells to continue dividing indefinitely is of huge concern. The unregulated growth of ES cells may generate tumors. This issue must be fully explored before clinical trials can proceed in humans.

A lot more basic information about stem cells and their behavior is required before they can be used to develop treatments. Consequently, the prospect of full clinical trials for any disease or condition is still some way off. The EuroStemCell project aims to contribute to the development of new treatments as rapidly as possible.