Stem cell biology
Overview
Stem cells have become the subject of widespread attention due to the potential human health benefits they offer. In particular, embryonic stem (ES) cells can turn into all the cell types that compose complex organisms, and it is possible that they may be made to do this under specifically controlled laboratory conditions. The great hope of stem cell biology is that one day these cells may be used to reconstruct the organs and cell systems in patients with dead or damaged tissue - for example, spinal cord damage.
What is a stem cell?
It may come as a surprise to learn that the adult body contains many stem cell populations. In fact, just under the surface of your skin lie a stockpile of stem cells that continually replaces the skin epidermis. These skin stem cells divide so that one daughter cell remains a stem cell and the other becomes committed to differentiation into a skin cell and migrates to the skin surface. It is the unique combination of these two properties, self-renewal and differentiation, which distinguishes stem cells from other somatic (mature) cells. At the head of this class is a group of very special stem cells from which all others are derived; known as ES cells which have the capacity to differentiate into all cells of the body and as a result are commonly referred to as being pluripotent (pluri, many). All other stem cells are known as adult stem cells. These have been less extensively studied as they may have limited differentiation capacity.
How do we get embryonic stem cells?
Although ES cells were isolated from mice two decades ago, it was not until 1998 that human ES cells were isolated and maintained in culture. ES cells are usually derived from the inner cell-mass cells of a blastocyst (one-week embryo). In the blastocyst, the inner cell-mass cells give rise to all the tissues of the developing foetus. Surplus embryos donated by couples undergoing IVF treatment are used for the derivation of human ES cell lines. Once removed from the embryo the ES cells are propagated in a culture dish supported by a layer of 'feeder' cells which help maintain their continual undifferentiated growth.
Controlling embryonic stem cells
The ability to direct an ES cell into a specific mature cell will help scientists to understand the natural development and function of cells and organs in mammals. However, controlling the differentiation of ES in vitro cells is an ongoing challenge facing ES researchers. Once removed from the tightly regulated growth conditions of the embryo, ES cells tend to differentiate spontaneously, often into undesirable cell types. For example the researcher may be aiming to get cardiac cells but other non-cardiac cells are produced. However, limited success has been achieved through manipulating the ES cell culture conditions, including the addition or removal of certain growth factors from the culture media. In 2000, researchers from Monash University in Melbourne, Australia, were the first to direct the differentiation of human ES cell lines into somatic cells. This was achieved by growing the ES cells in conditions which limit stem cell renewal, and blocked differentiation into extraembryonic tissue. Since then ES cells have been coaxed into cells such as cardiac muscle and various epithelial cell layers.
Applications of stem cell biology
The controlled growth and differentiation of ES cells into specific tissue types may lead to the creation of new healthy cells to replace damaged tissue. Current research is focused on the production of pancreatic islet cells for alleviating diabetes and ES derived neuronal cells that may repopulate and repair damaged areas of the brain in patients suffering diseases such as Parkinson's Disease and Alzheimer's Disease. Stem cell therapy may also have application in delivery of healthy genes to organs with a missing or defective gene.
One area of concern for cell therapy scientists is the potential problem of immune rejection that has always plagued organ transplant medicine. Therapeutic cloning aims to create ES cells that are genetically, and therefore immunologically, matched to the patient by using a similar cloning technique to the one used to create Dolly the sheep. A cell from a patient would be fused with an egg obtained from a donor, from which the chromosomes had been removed (enucleated oocyte). This embryo would then be allowed to grow to the blastocyst stage from where ES cells are harvested. These could then be coaxed into the specific cell type required for repair of the patient's original tissue lesion. For example, patients suffering from Parkinson's Disease suffer from a loss of dopaminergic neurons, so the ES researcher would be aiming to make neurons that produce dopamine, or a precursor of dopamine.
 Therapeutic cloning: a simplified example - A cell, such as a skin cell, biopsied from a spinal cord injury patient, is fused with an enucleated oocyte. The resulting cloned embryo is induced to grow to the blastocyst stage from which ES are cells derived. These cells would be differentiated to neurons for transplantation to the patient. As the nucleus of the transplanted cell is identical to the cells of the patient, rejection would not be an issue.
Ethics, legislation and regulation
The debate on moral issues surrounding the derivation of ES cells has meant that governments have responded with strict regulations regarding the creation and manipulation of these cells. Currently, US researchers seeking government funding must use ES cell lines derived before 2001 and no more ES cell lines may be produced for research purposes. In Australia, federal legislation passed in December 2002 allows ES cell research and the creation of ES cell lines from surplus IVF embryos. In the European Union however, therapeutic cloning has been given the green light since November 2001. In Australia, there is currently a ban on therapeutic cloning, which attracts a 15-year jail term.
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