Stem cells – gateway to 21st century medicine
Key text
This topic is sponsored by the National Centre for Advanced Cell Engineering Facility.
Human embryonic stem cells burst into the headlines in 1998 and have made regular appearances ever since. Newspapers love controversy. But why is the issue so controversial?
Stem cells promise to be a powerful new technology that can't be ignored. Proponents say they will revolutionise medicine, while opponents call them Frankenstein technology. Just what are these headline-making cells?
What are stem cells?
Most of the 300 trillion cells of the body have completely specialised functions. Blood, lung, brain, skin or liver cells are all wonderfully specialised for what they do. By and large, they cannot do anything other than what they were designed for. Stem cells, on the other hand, do not have a specialised function; they are an immature kind of cell that still has the potential to develop into many different kinds of cell. They are 'all-purpose' cells.
There is another characteristic of stem cells that makes them so prized. Unlike our specialist cells, stem cells have the capacity to keep multiplying. This capacity to both proliferate and form different types of cells makes them ideal for replacing damaged tissue. Need new pancreatic cells to replace the ones you've lost to diabetes? Let stem cells churn them out for you. And being human cells, stem cells could also be used to study disease development, to test new drugs on human tissues and to trial different ways of treating disease.
That's the potential of stem cells and the reason why research scientists, biotech companies and sick people are so passionate about having the freedom to develop that potential.
Types of stem cells
Related site: How embryonic stem cell lines are made
An animation showing the basic processes involved in establishing human stem cell lines.
(DNA Learning Center, USA)
Scientists distinguish between several types of stem cells.
Embryonic stem cells are obtained from surplus 5-day-old embryos. Such embryos are produced in the 'test-tube' for infertile couples, but often more are produced than needed. These surplus embryos are stored in the freezer and normally thrown away after 5 years. Embryonic stem cells, derived from surplus embryos, can be programmed to become any cell of the body (they are pluripotent). They also have the capacity to keep proliferating indefinitely in a culture dish.
Embryonic germ stem cells come from six to nine week old embryos, from cells that would normally develop into eggs or sperm. Like embryonic stem cells they can develop into any cell type. Unfortunately though embryonic germ cells don’t keep dividing for as long as embryonic stem cell lines when cultured, so they may not be as suitable for research.
Adult stem cells exist in mature tissues and supply the tissue with replacement cells throughout life. For instance, our blood stem cells churn out 5 million cells per second! Until recently, only tissues like blood and skin, which replace themselves prodigiously, were thought to have stem cells. Now it seems that whichever organ researchers look at, they find stem cells, even when those organs don't seem to be very good at replacing their lost cells, like the brain or pancreas.
Compared to embryonic stem cells, which can make replacement cells for any tissue, adult stem cells are normally dedicated to making the cells for one particular tissue. For instance, skin stem cells usually can only make skin, not brain or blood. And when isolated and placed in the culture dish, they don't grow indefinitely as embryonic stem cells do.
Umbilical cord stem cells are collected from umbilical cord blood and can make a limited number of different cell types (they are multipotent).
More recently, stem cells have been developed that have the benefits of embryonic stem cells – they keep dividing and can form a range of cell types – but are made using normal adult cells (like skin cells). One way of doing this is to insert the nucleus from an adult cell into an egg that has had its nucleus removed (somatic cell nuclear transfer). The egg then develops into an embryo yielding embryonic stem cells that are matched to the adult cell donor. Another technique does away with eggs altogether and reprograms adult cells to behave like embryonic stem cells (induced pluripotent stem cells). Both technologies have only recently been used to produce human cells and will need extensive research before they can be used therapeutically.
Producing stem cells from embryos and somatic cell nuclear transfer (Click on image for a larger version)
(Image: Australian Stem Cell Centre)
Cures from stem cells
Type 1 diabetes and Parkinson's disease are seen as good candidates for stem cell therapy. Both diseases cause the loss of a relatively small amount of tissue. In juvenile diabetics, the insulin-producing cells of the pancreas are destroyed by the immune system. In Parkinson's disease the dopamine-producing cells of the brain are destroyed – no-one really knows why. Researchers have already had some success treating patients by replacing the lost tissue with material from aborted fetuses (in the case of Parkinson's disease) or donated pancreases (in the case of type 1 diabetes).
Related site: Cloning around with stem cells
Describes how stem cells could be used to treat diseases such as diabetes.
(The Slab, Australian Broadcasting Corporation)
But aborted fetuses and donated organs are not the solution to the problem. Not only is the quality of these tissues unreliable, but the amount available is a drop in the bucket compared to the numbers of patients who would benefit from stem cell therapy. It has already been shown to work in mice suffering from symptoms of Parkinson's disease. In time, human stem cells might provide an endless supply of high quality material to treat all patients.
Most researchers believe it is essential to carry out research on both embryonic and adult stem cells. Both have advantages and drawbacks. Researchers cannot yet say which types of cells will work best. In general, the advantage of starting with embryonic stem cells is that they can be grown in large quantities, but at some point the researcher has to train these cells to become dopamine-producing brain cells or insulin-producing pancreatic cells, and that is the difficult part.
On the other hand, adult stem cells taken from the brain or pancreas are already programmed to make brain or pancreas cells. The problem is they don't grow very well in the culture dish. And it is difficult to procure spare adult stem cells. At the moment, researchers use cadavers to obtain brain and pancreatic stem cells.
The biological hurdles to stem cell therapy
Although progress is being made and the technology is rapidly changing, it will take another 10 to 15 years of development and testing before many proposed applications of stem cells will be used. Any stem cell therapy will have to clear several hurdles.
Immune rejection
The first hurdle to clear is immune rejection. Patients receiving a graft of embryonic
stem cells or adult stem cells sourced from cadavers would probably be treated
in much the same way that organ transplant recipients are treated. The grafts
would be matched to the individual patient and anti-rejection drugs would be
used. Patients receiving brain cells may not need these drugs; the brain seems
to get away with less surveillance by the immune system than other parts of the
body. And there is one type of stem
cell known as a mesenchymal stem cell that seems to evade detection by
the immune system. Everyone carries mesenchymal stem cells in their bone
marrow; they normally give rise to cartilage, bone or muscle cells. If these
cells do not trigger immune rejection they could be used in future treatments
of bone and joint diseases or repair heart muscle damaged during a heart
attack.
If patients provide their own stem cells, then of course immune rejection is no problem. Leukaemia patients routinely rely on their own stem cells. A reserve of their blood-forming stem cells (found in bone marrow, but different from mesenchymal stem cells) is stored away. After cancer therapy, which destroys stem cells, patients rely on the stored stem cells to rapidly restore their red and white blood cell counts to normal. Burn patients rely on the stem cells present in a tiny square patch of skin to seed the growth of metres of new skin in the culture dish.
Cancer
Any stem cell, adult or embryonic, has the ammunition
it needs to give rise to cancer: an explosive ability to grow and to change
into other types of cells. In fact,
researchers now realise that at the heart of many common cancers lies an adult
stem cell gone awry.
Any stem cell lines injected into patients have to be carefully tested first in animals to see if they give rise to cancer. Though cautious, researchers believe they will be able to tame the tendency of stem cells to form cancers. Embryonic germ stem cells may be useful in this regard as they do not seem to cause tumours.
Opposition to embryonic stem cell research
Some people oppose embryonic stem cell research on religious grounds. Many Catholics, for instance, take the view that from the moment of conception an embryo is a human being with a soul, and that using these embryos is like dismembering a person. But not all religious people take this view. Some believe that an individual human being does not truly arise until the embryo has implanted into the wall of the mother's womb at around 14 days. According to that view, these embryos are too primitive to be to considered human beings and so it is not unethical to use them for life-saving research, especially if they are to be thrown away in any case.
Some people even argue it is unethical NOT to use embryonic stem cells to search for cures for diseases. Though no-one can guarantee that such research will be successful, embryonic stem cells offer new hope. As with many problems of ethics, it comes down to balancing the needs of one party versus another. In this case it is a matter of weighing the hopes of sick people for a cure against the beliefs of another group of people.
Some people are fearful of human embryonic stem cell research, because they see it as yet another step on the slippery slide that will lead to widespread human cloning. In the public mind, the techniques for cultivating embryonic stem cells seem linked to cloning, but they are actually separate technologies. Researchers could happily go ahead developing embryonic stem cells to provide replacement tissue for patients without ever touching cloning techniques.
But having said that, some researchers are looking into combining cloning techniques with embryonic stem cell culture techniques through somatic cell nuclear transfer (SCNT). This is not for the purpose of cloning an individual, but for growing tissue that is perfectly matched to a patient (therapeutic cloning). This would eliminate the need for life-long use of anti-rejection drugs.
Stem cells and cloning legislation
After extensive debate, the Australian Parliament passed legislation in 2002 that regulates embryonic stem cell research and cloning (Box 1: How has stem cell research been legislated in Australia, the US and the UK?). This was amended in 2006 as research and attitudes changed. But because new developments are emerging all the time, legislation is hard pressed to keep up. In 2008 a Californian group announced the production of an early embryo from human skin cells, opening up the door to patient specific stem cell therapy. Under Australia’s 2002 legislation the Californian experiment would have been illegal.
Box
1. How has stem cell research been legislated in Australia, the US and the UK?
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Page updated July 2009.