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Stem cells – gateway to 21st century medicine
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 tissue that is lost. Need new pancreatic cells to replace the one you've lost to diabetes?  Let stem cells churn them out for you. 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.

Two 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 two types of stem cells: embryonic stem cells and adult 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 also have the capacity to keep proliferating indefinitely in a culture dish.

Adult stem cells exist in certain 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.  

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.  

Two biological hurdles to stem cell therapy

Any stem cell therapy will have to clear two 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.

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 would like to combine cloning techniques with embryonic stem cell culture techniques – not for the purpose of cloning an individual, but for growing replacement tissue that is perfectly matched to a patient. 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. The legislation is more liberal than that of the United States legislation, but stricter than that of the United Kingdom (Box 1: How has stem cell research been legislated in Australia, the US and the UK?). But because new developments are emerging all the time, legislation is hard pressed to keep up. For example, in August 2003 researchers in China reported using rabbit eggs to carry out human 'therapeutic cloning'.  The eggs were used to reprogram human skin cells to become embryos. Once embryos had formed, researchers cultivated stem cells from them. Under Australia's current legislation, the Chinese experiment would be illegal.

Box

1. How has stem cell research been legislated in Australia, the US and the UK?

Related Nova topic:

The mammal copiers – advances in cloning
Explains the difference between whole animal cloning and cloning to produce tissues and organs for the treatment of damaged or diseased tissue and organs.

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Posted October 2003.

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