Stem cells are the foundation cells for every organ, tissue and cell in the body. They are like a blank microchip that can ultimately be programmed to perform particular tasks. Stem cells are undifferentiated or “blank” cells that have not yet fully specialized. Under proper conditions, stem cells begin to develop into specialized tissues and organs. Additionally, stem cells can self-renew, that is they can divide and give rise to more stem cells.
There are many different types of stem cells. These include embryonic stem cells that exist only at the earliest stages of embryonic development; as embryonic stem cells can form all cell types of the body, they are referred to as ‘pluripotent’ stem cells. There are various types of ‘adult’ or ‘tissue-specific’ stem cells that exist in a number of different fetal and adult tissues. These stem cells generally can only form a limited number of cell types corresponding with their tissues of origin; they are called ‘multipotent’ stem cells.
Embryonic stem cells are derived from the inner cell mass of a blastocyst: the fertilized egg, called the zygote, divides and forms two cells; each of these cells divides again, and so on. Soon there is a hollow ball of about 150 cells called the blastocyst that contains two types of cells, the trophoblast and the inner cell mass. Embryonic stem cells are obtained from the inner cell mass.
Stem cells can also be found in small numbers in various tissues in the fetal and adult body. For example, blood stem cells are found in the bone marrow that give rise to all specialized blood cell types. Such tissue-specific stem cells have not yet been identified in all vital organs, and in some tissues like the brain, although stem cells exist, they are not very active, and thus do not readily respond to cell injury or damage.
Stem cells can also be obtained from other sources, for example, the umbilical cord of a newborn baby is a source of blood stem cells. Recently, scientists have also discovered the existence of cells in baby teeth and in amniotic fluid that may also have the potential to form multiple cell types. Research on these cells is at a very early stage.
Recently, cells with properties similar to embryonic stem cells, referred to as induced pluripotent stem cells (iPS cells) have been engineered from somatic cells (see ‘What is are induced pluripotent stem cells?’).
A stem cell line is a population of cells that can replicate themselves for long periods of time in vitro, meaning outside of the body. These cell lines are grown in incubators with specialized growth factor-containing media (liquid food source), at a temperature and oxygen/carbon dioxide mixture resembling that found in the mammalian body.
Embryonic stem cells are those grown from the cells that make up the inner cell mass of the blastocyst. Embryonic stem cells have been derived from a variety of animals, including human, and are described as ‘pluripotent’- that is, they are capable of generating any and all cells in the body under the right conditions.
Embryonic stem cell lines can be grown indefinitely in vitro if the correct conditions are met. Importantly, these cells continue to retain their ability to form different, specialized cell types once they are removed from the conditions that keep them in an undifferentiated, or unspecialized, state.
The most widely studied are mouse embryonic stem cells. Mouse embryonic stem cells have taught us a lot about how pluripotent cells grow and specialize, and how embryonic development works. Indeed, mouse embryonic stem cells are a critical research tool for studying the function of individual genes and modeling human diseases. Mouse embryonic stem cells can be manipulated to contain specific genetic changes then used to generate mice which contain this change. Capecchi, Evans and Smithies were awarded the Nobel Prize in Physiology or Medicine, 2007 for developing this process.
Human embryonic stem cells were isolated relatively recently, in 1998. They are more difficult to work with than their mouse counterparts and currently less is known about them. However, scientists are making remarkable progress, learning about human developmental processes, modeling disease and establishing strategies that could ultimately lead to therapies to replace or restore damaged tissues using these human cells.
Perhaps better referred to as a tissue-specific stem cell, these cells are found in tissues that have already developed. Tissue-specific stem cells can be isolated from many tissues, including brain. The most common source of tissue-specific stem cells is the bone marrow, located in the center of some bones. There are different types of stem cells found in the bone marrow, including hematopoietic or blood stem cells, endothelial stem cells, and mesenchymal stem cells. It is well established that hematopoietic stem cells form blood, that endothelial stem cells form the vascular system (arteries and veins), and that mesenchymal stem cells form bone, cartilage, muscle, fat, and fibroblasts.
While it has been theorized that some adult stem cells may have a broader potential to form different cell types than was previously suspected (for example, cells from the bone marrow may contribute to regeneration of damaged livers, hearts and other organs), this is highly controversial in the scientific community. Currently, it is not clear whether stem cells from adult tissues or umbilical cord blood are truly pluripotent. The comparison of human embryonic stem cells to adult stem cells is currently a very active area of research.
Induced pluripotent cells (iPS cells) are non-pluripotent cells that were engineered (‘induced’) to become pluripotent, that is, able to form all cell types of the body. In other words, a cell with a specialized function (for example a skin cell) was ‘reprogrammed’ to an unspecialized state similar to that of an embryonic stem cell. While iPS cells and embryonic stem cells share many characteristics they are not identical.
The generation of mouse iPS cells was reported in 2006 Currently, iPS cells are produced by inserting copies of three-four genes into specialized cells known to be important in embryonic stem cells using viruses. Different groups have used slightly different combinations of genes. It is not completely understood how each of these genes functions to confer pluripotency and ongoing research is addressing this question.
The technology used to generate iPS cells holds great promise for creating patient- and disease-specific cell lines for research purposes. However, a great deal of work remains before these methods can be used to generate stem cells suitable for safe and effective therapies.
Stem cell research contributes to a fundamental understanding of how organisms develop and grow, and how tissues are maintained throughout adult life. This is knowledge that is required to work out what goes wrong during disease and injury and ultimately how these conditions might be treated. The development of a range of human tissue-specific and embryonic stem cell lines will provide researchers with the tools to model disease, test drugs and develop increasingly effective therapies.
Replacing diseased cells with healthy cells, a process called cell therapy, is a promising use of stem cells in the treatment of disease; this is similar to organ transplantation only the treatment consists of transplanting cells instead of organs. Currently, researchers are investigating the use of adult, fetal and embryonic stem cells as a resource for various, specialized cell types, such as nerve cells, muscle cells, blood cells and skin cells that can be used to treat various diseases.
In theory, any condition in which there is tissue degeneration can be a potential candidate for stem cell therapies, including Parkinson’s disease, spinal cord injury, stroke, burns, heart disease, Type 1 diabetes, osteoarthritis, rheumatoid arthritis, muscular dystrophies and liver diseases.
In addition, retinal regeneration with stem cells isolated from the eyes can lead to a possible cure for damaged or diseased eyes and may one day help reverse blindness. Bone marrow transplantation (transfers blood stem cells) is a well-established treatment for blood cancers and other blood disorders.
Here are just a few of the challenges that lie ahead. Firstly, a source of stem cells must be found. The process of identifying, isolating and growing the right kind of stem cell, for example a rare cell in the adult tissue, is painstaking. In general, embryonic and fetal stem cells are believed to be more versatile than tissue-specific stem cells. Secondly, once stem cells are identified and isolated, the right conditions must be developed so that the cells differentiate into the specialized cells required for a particular therapy. This too will require a great deal of experimentation. Thirdly, a system that delivers the cells to the right part of the body must be developed and the cells once there must be encouraged to integrate and function in concert with the body’s natural cells. Furthermore, just as in organ transplants, the body’s immune system must be suppressed to minimize the immune reaction set off by the transplanted cells.
While results from animal models are promising, the research on stem cells and their applications to treat various human diseases is still at a preliminary stage. As with any medical treatment, a rigorous research and testing process must be followed to ensure long-term efficacy and safety.