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Advances and challenges in the therapeutic use of stem cells.

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Stem cells are early cells from which all other cells develop. They are without specific function but under given conditions will differentiate to become any one of the body’s many cell types. They serve as the basis for the development of the foetus, and as a resource for repair of damaged tissue later in life.


VOL: 101, ISSUE: 45, PAGE NO: 21

Catriona Gilmour Hamilton, RGN, is special projects manager, Lymphoma Association

Stem cells are early cells from which all other cells develop. They are without specific function but under given conditions will differentiate to become any one of the body’s many cell types. They serve as the basis for the development of the foetus, and as a resource for repair of damaged tissue later in life.



Stem cells in research
Adult stem cells are considered to be multipotent. This means that they are programmed to grow into the differing cells of a particular part of the body, typically the cells of the tissue in which they are found.



Embryonic stem cells are present in the inner cell mass of the blastocyst, a ball of around 150 cells present within a few days of conception. Embryonic stem cells are pluripotent. This means that they have unlimited potential to grow into any cell type.



Many researchers believe that, because they are pluripotent, embryonic stem cells have greater research potential than multipotent adult stem cells. However, recent research suggests that adult stem cells might have greater potential for differentiation than initially suspected.



The consensus is that there is far more to be done in understanding the potential of stem cells. Adult stem cells are found in very limited quantities in a relative few places, and the process of identification and culture can be painstaking. There are also concerns that the relative old age of adult stem cells means that they have greater potential for disease or dangerous genetic mutation.



Stem cells have also been found in umbilical cord, amniotic fluid and deciduous (milk) teeth. More research is needed to find out their full potential for differentiation, but these may prove to be a richer supply of adult stem cells that are younger, more vigorous, and easier to culture in stem cell lines.



Stem cell lines
Stem cell lines are populations of cells that have grown from an original stem cell. These populations provide stem cells for research. They reproduce themselves for long periods of time under controlled laboratory conditions that mimic the mammalian body environment. They are, in theory, immortal because the cells will continue to divide and replenish supply.



Current therapy
Adult haematopoetic stem cells - the cells from which blood tissue cells grow - are the best understood of human stem cells and have been used in therapeutic applications for some time.



A typical example is the use of peripheral blood stem cell transplant used in the treatment of cancers, such as lymphoma, for well over a decade. Stem cell transplant means that high dose myeloeblative therapy can be given to treat lymphomas that do not respond to regular treatment, that relapse following initial therapy or that have a high tendency to relapse.



Stem cells are harvested from the peripheral blood, following treatment with stimulant growth factors, and stored for retransfusion after high dose therapy. Through a process of ‘stem cell homing’ the reinfused cells find their way from the blood stream to the bone marrow and begin the process of replenishing myeloid tissue and blood cells.



It is suspected that haematopoetic stem cells have the potential to transdifferentiate - to grow into cells other than bone marrow and blood. This is also referred to as plasticity. Clinical trials designed to explore this potential have used infusions of stem cells in a variety of disease settings.



For example, several studies have used bone marrow stem cells to restore the heart muscle following myocardial infarction. Such applications remain experimental but could lead to more diverse use of adult stem cells in the future.



The future
The most widely publicised application of stem cell research is the growth of replacement tissues. Of particular interest have been tissues that, until relatively recently, have been considered difficult or impossible to replace once damaged - tissues such as heart, liver, brain and spinal cord.



According to the International Society for Stem Cell Research (ISSCR): ‘Any disease in which there is tissue degeneration can be a potential candidate for stem cell therapies, including Parkinson’s and Alzheimer’s diseases, spinal cord injury, stroke, burns, heart disease, type 1 diabetes, osteoarthritis, rheumatoid arthritis, muscular dystrophies and liver diseases’ (2005). Table 1 offers a few examples of the kind of research taking place.



Stem cell research is not only about replacement cells. Study into stem cells is also undertaken in order to understand cellular development and gain further understanding of disease processes. These applications may lead to prevention of birth defects, slowing of progression of disease and better treatment of debilitating illnesses.



An example of this kind of stem cell research is in motor neurone disease (MND). Scientists at the Roslin Institute in Edinburgh have generated stem cell lines using DNA from patients with MND. They can closely observe the behaviour and chemical profile of these cells, identifying the factors that contribute to cell death and testing new medicines (Hopkins Tanne, 2005a).



Research into stem cell behaviour might also enhance capacity to heal, for example, utilising the brain’s own supply of stem cells to repair neurological damage as a result of stroke, trauma or multiple sclerosis. However, this advance requires a greater understanding of what triggers the repair process (Hopkins Tanne, 2005b).



The challenge ahead
The challenges of the immediate future - the scientific, the ethical and the political - seem monumental. Individuals including Professor Sir Robert Winston have asked whether the potential of stem cell research has been overstated, and the difficulties understated (Amos, 2005).



The most pressing scientific challenges can be summarised as follows:



- More needs to be learnt about adult stem cells - their real potential for transdifferentiation, and how adult stem cells can be better identified and cultured;



- Researchers need greater understanding of the process of cell differentiation - what factors influence it, and how it might be influenced in a controlled and managed way;



- The process of differentiation of embryonic stem cells is potentially hazardous - stem cell lines may acquire harmful genetic mutations, or viruses, over time - there is a demonstrated risk of tumour formation as a result of uncontrolled rapid growth of undifferentiated cells;



- The function of new tissues must be maintained within, and adequately integrated with, the patient’s body. For example, heart muscle cells that beat in the laboratory must beat in time with the patient’s own heart muscle cells;



- The problem of tissue rejection must be overcome, as the patient’s immune system will reject transplanted cells.



The ethical issues



An important issue for stem cell research is where the original cells come from, and both embryonic and adult stem cells have their limitations.



Embryonic stem cells come from embryos created for in-vitro fertilisation treatment. After a cycle of IVF, some embryos are left surplus to requirements. The couple can then consent to donate the embryos for research purposes.



The extraction of stem cells means that the embryo dies. This means that embryonic stem cell research is troubling to many people on moral and ethical grounds.



Scientific progress is made infinitely more complex in light of the bioethical context of stem cell research. Put simply, do the potential ends justify the means? Two of the most sensitive aspects of stem cell research are the use of cloning and the question of the human status of the embryo.






A potential solution to the problem of tissue rejection is the use of cloning technology. Somatic cell nuclear transfer is a process in which the nucleus from one of the recipient’s cells, such as a skin cell, is used to replace the nucleus of an egg. Using an artificially induced process of parthenogenesis - in which the egg develops without fertilisation - the egg is grown to blastocyst stage and stem cells taken. The cells and tissues resulting from this have an identical genetic make-up to the eventual recipient. In this way, the risk of tissue rejection can be overcome.



Such technology is known as therapeutic cloning - cloning to produce cells for research purposes. Supporters are keen to stress the difference between this and reproductive cloning, which is intended to produce a new individual.



But critics of the technology remain very concerned at the fineness of the line between the two, and are fearful of the precedent that might be set by the legalisation of cloning technology regardless of its intention. Currently the UK supports licensed use of therapeutic cloning but the EU and the US do not.



The ‘right to life’ argument



The bioethical question at the heart of embryonic stem cell research is the definition of human life itself - at what precise point after fertilisation does a human being exist? Is an embryo entitled to the same consideration as a fully formed human being? Does a fertilised egg have a soul?



Pro-life organisations, Christian and other religious groups equate embryonic stem cell research with murder. They argue that the embryo has the same entitlement to protection as any other human being, and that the potential medical benefits of embryonic stem cell research do not in any way justify what they describe as the mass murder of unborn individuals.



To counter this argument, those in favour of embryonic stem cell research argue that embryos that are surplus to fertility requirements will be discarded eventually anyway, that they are donated with consent and that to waste such a rich source for medical advancement is immoral. They stress that embryos used in this way are younger than 14 days, the point at which the brain begins to develop.



Moral resistance to the destruction of embryos carries an enormous political weight. This is the view held by US president George W Bush - meaning that US federal funding for stem cell research is currently restricted to that from stem cell lines derived prior to August 2001. This has put a halt on funding for research with new stem cell lines, with what many fear to be serious scientific and commercial consequences. This article has been double-blind peer-reviewed.



For related articles on this subject and links to relevant websites see

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