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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?
Contents

Key text

Box 1. How has stem cell research been legislated in Australia, the US and the UK? Activities
Further reading
Useful sites
Glossary

Key text

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 almost 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.

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 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 (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?

Australia

In December 2002, Australia passed two pieces of federal legislation to regulate cloning and embryonic stem cell research The first, Prohibition of Human Cloning Act 2002, outlawed any form of human cloning, whether it be to generate tissues (therapeutic cloning) or a new human being (reproductive cloning). The second, Research Involving Human Embryos Act 2002, allowed researchers to access surplus human embryos, under strict conditions.

A major objection to stem cell research, from both religious and non-religious groups, is that it devalues human life because it uses embryos as 'a means to an end'. For that reason Australia's legislation ensured that embryos could not be created for the sole purpose of harvesting their stem cells. Then in 2006 legislation was passed allowing therapeutic cloning to develop stem cells for research and ultimately therapy.

Scientists wanting to use therapeutic cloning (or somatic cell nuclear transfer) must first obtain a licence from the National Health and Medical Research Council.

United States

In the US, government-funded researchers have not been allowed to make stem cells from spare human embryos. But there is no criminal law against it; so researchers in private companies have not had the same constraints as researchers receiving government funding. Government-funded scientists say the US effort is falling behind because of the restrictions placed on them. 

At present, these government-funded researchers have access to only nine embryonic stem cell lines. Five of which came from Australia. Although this will change with the 2009 announcement that embyonic stem cell restrictions will be lifted. Scientists think that more cell lines are needed for a number of reasons. For example, additional cell lines would provide more genetic diversity, they would be a source of replacements in case problems develop with existing cell lines, and they could serve as sterile lines for future cell-based therapy.

United Kingdom

The House of Commons (December 2000) and the House of Lords (January 2001) voted in favour of permitting research using human embryonic stem cells and approved the creation of embryos for specific research purposes. Under strict licensing the relevant legislation allows research involving human embryos that have not exceeded the fourteenth day of their development. The Human Fertilisation and Embryology Authority has regulatory responsibility and will not licence any research that has reproductive cloning as its aim.

Related sites

  • Parliament of Australia

  • Human embryos and cloning (National Health and Medical Research Council, Australia)

  • The United Kindom Parliament

  • Report for Congress – stem cell research (United States House of Representatives)

    Activities

  • Biotechnology Online (CSIRO, Australia)

  • Genetics Science Learning Center (University of Utah, USA)
    • Stem cells – provides a range of different activities relating to stem cells. Activities include 'What are some different types of stem cells?'; 'What are some issues in stem cell research?' and 'What is a stem cell?'.

  • National Center for Case Study Teaching in Science (University of Buffalo, USA)

  • Daily Lesson Plan (New York Times Learning Network, USA)

  • Stem cells (Nova ScienceNow, USA)
    • Teachers guide - students view a 15 minute video, review what they know about stem cells and explore the ethics of stem cell research.

    Bioethics Outreach (Iowa State University, USA)

    The orphan embryos: A case study in bioethics – provides a case study and a series of questions.

    Further reading

    ATSE Focus
    A number of articles related to stem-cell technology is available.

    Australasian Science

    July 2009, page 11
    Stem cell hope for corneal blindness
    Describes successful treatment of eye conditions by delivering stem cells on a contact lens.


    July 2008, page 12
    Memory stem cell found (by Stephen Luntz)
    Reports on the discovery of stem cells in the brain’s hippocampus.

    November-December 2006, pages 16-18
    Stem cells linked to breast cancer (by Mark Shackleton)
    Looks at how cellular mechanisms may explain the prominence of breast cancer.

    August 2006, pages 31-32
    Government pays lip service to stem cell debate (by Simon Grose)
    Examines the politics of stem cell research in Australia.

    Cosmos
    7 March 2009
    Brief guide to stem cells
    Outlines what stem cells are and the likely changes to restrictions in embryonic stem cell research in the USA.

    November 2005
    Hard cell (by Ronald Bailey)
    Looks at some of the moral dilemmas created by embryonic stem cell research.

    Issues
    March 2009, pages 46-48
    Stem cells: ethics versus patient needs (by Natalie Seach, Veronica Shannon and Richard Boyd)
    Examines the current status of stem cell research as well as the ethical issues associated with stem cells.

    Nature
    A collection of articles on making stem cells is available.

    1 July 2009, pages 18-19
    How to fix a broken heart? (by Monya Baker)
    Describes research into potential treatments for heart disease using stem cells.

    23 April 2009, pages 962-965
    Stem cells: Fast and furious (by Monya Baker)
    Covers the development of stem cells from body cells (induced pluripotent stem cells).

  •  

    New Scientist
    A collection of New Scientist articles on cloning and stem cells is available.

    14 April 2009
    Stem cells free diabetics from insulin treatment (by Andy Coghlan)
    Reports on results of a controversial treatment for type-1 diabetes using stem cells.

     

    17 January 2009, pages 6-7
    DIY stem cells could help us heal ourselves (by Andy Coghlan)
    Describes a treatment that uses the body’s own stem cells to heal itself.

     

    18 June 2008, pages 8-9
    A cell’s destiny is no longer fixed (by Peter Aldhous)
    Reports on successful reprogramming of cells to produce stem cells.

     

    3 May 2008, pages 40-43
    How stem-cell advances will transform medicine (by Peter Aldhous)
    Proposes the use of stem cells to regenerate body parts.

     

    8 February 2008, page 11
    Stem cell transplant ‘cures’ diabetic mice (by Andy Coghlan)
    Looks at the use of transplants derived from stem cells to reverse diabetes.

     

    8 December 2007, page 10
    Stem cells shots restore lost memory (by Andy Coghlan)
    Reports of experiments which suggest stem cells injections may help restore memory.

     

    22 September 2007, page 20
    Human stem cells from adult cells move a step closer
    Reports on development towards deriving human stem cells from adult cells.

     

    13 June 2007, pages 14-15
    Stem cell genes may provide medicine’s dream ticket (by Peter Aldhous)
    Explores the potential of treating diseases with therapeutic genes inserted into stem cells.

     

    6 June 2007, pages 8-9
    Stem cells: from adult to embryo (by Jessica Marshall and Linda Geddes)
    Reports on a technique that made stem cells from adult cells.

     

    10 April 2007
    'Rebuilt' immune system shakes off diabetes (by Roxanne Khamsi)
    Reports on a one-off treatment for diabetes.

     

    13 January 2007, page 9
    Amniotic fluid supplies ‘repair kit’ for later life
    Reports that stem cells have been discovered in amniotic fluid.

     

    15 November 2006, page 12
    Stem cells reverse muscular dystrophy (by Debora Mackenzie)
    Reports that stem cells have helped dogs with muscular dystrophy to walk again.

     

    7 October 2006, pages 8-9
    Organs on demand, no embryo needed (by Bruce Goldman and Andy Coghlan)
    Looks at the creation of personalised stem cells that may offer a way around ethical objections.

     

    11 March 2006, pages 38-41
    Miracle postponed (by Peter Aldhous)
    Discusses the skepticism surrounding some claims made by stem cell researchers.

     

    31 January 2006
    Stem cell transplants offer hope against lupus (by Roxanne Khamsi)
    Describes the use of a patient’s own stem cells to treat lupus.

     

    22 October 2005, pages 10-11
    Are all embryos created equally? (by Andy Coghlan)
    Describes two new ways of creating embryonic stem cells, that do not harm embryos.

     

    25 May 2005, pages 8-9
    Double triumph in stem cell quest (by Michael Le Page and Rowan Hooper)
    A Chicago team is claiming it has found an easier route to embryonic stem cells.

     

    Scientific American
    January 2008, page 35
    Stem cell control (by Christine Soares)
    Reports on research altering the characteristics of embryonic stem cells.

     

    July 2006, pages 35-41
    Stem cells: The real culprits of cancer? (by Michael Clarke and Michael Becker)
    Looks at the ability of stem cells to become malignant as the potential cause of cancer and summarises the possible paths to cancer.

     

    June 2004, pages 60-67
    The stem cell challenge (by Robert Lanza and Nadia Rosenthal)
    Looks at the hurdles that stand between the promise of human stem cell therapies and real treatments in the clinic.

     

    Useful sites

    Stem cell channel (Australian Stem Cell Centre)

    Clearly covers a range of issues in stem cell research using video. Fact sheets are also provided on topics including the ethics of stem cell research, types of stem cells and Australian research.
    http://www.stemcellchannel.com.au/

     

    Stem cells in the spotlight (Genetic Science Learning Center, USA)

    A clearly presented coverage of stem cells. 'What is a stem cell?' uses a humorous animation to introduce stem cells. Other topics include 'What are some different types of stem cells?'; 'Stem cell therapies: What is the recipe for success?' and 'Creating stem cells for research'.
    http://gslc.genetics.utah.edu/units/stemcells/

     

    National Institutes of Health, USA

    Stem cell information: Stem cell basics
    More in-depth information about stem cells, presented as a series of questions and answers.
    http://stemcells.nih.gov/info/basics/

     

    Stem cell reports: Regenerative medicine
    Explores cutting edge research involving stem cells.
    http://stemcells.nih.gov/info/scireport/

    Stem cells: The all round athletes (University of Wisconsin-Madison, USA)

    An educational video that highlights stem cell research, challenges and applications.
    http://www.wicell.org/index.php?option=com_content&task=blogsection&id=8&Itemid=155

    Human stem cell research (Australian Academy of Science)

    A report reviewing scientific and regulatory developments in human stem cell research during 2000-2001.
    www.science.org.au/reports/stemcell.pdf

    Stem cells for cell-based therapies (Actionbioscience.org)

    Describes progress in stem cell research and likely future therapeutic applications.
    http://www.actionbioscience.org/biotech/pecorino2.html

    Molecular mechanisms of stem-cell identity and fate (Nature.com, UK)

    A poster showing the origin of embryonic and adult stem cells.
    http://www.nature.com/nrc/posters/stemcell/stemcell_poster.pdf

    Stem cells and the future of regenerative medicine (National Academies Press, USA)

    A 2002 report summarises the findings of a workshop sponsored by the National Academies.
    http://books.nap.edu/openbook/0309076307/html/index.html

    Australian Broadcasting Corporation (transcripts)

    Australasian Science
    July 2009, page 11
    Stem cell hope for corneal blindness
    Describes successful treatment of eye conditions by delivering stem cells on a contact lens.

    Therapeutic cloning (Ask an Expert)
    Provides answers to ten common questions about therapeutic cloning.
    http://www.abc.net.au/science/expert/realexpert/cloning/

     

    From my father's fridge (Australian Story, 25 April 2005)
    The story of medical scientist, Professor Robert Tindle, who made a discovery that led to the use of stem cells to save thousands of lives around the world, including his own daughter.
    http://www.abc.net.au/austory/content/2005/s1355603.htm

     

    End of embryo ban a boon for scientists (The Lab, 5 April 2005)
    Australian scientists have a wider pool of human embryos to use for research from today with the lifting of a ban on using recently created embryos.
    http://www.abc.net.au/science/news/health/HealthRepublish_1338622.htm

    Why stem cells make for risky business (The Australian Academy of Technological Sciences and Engineering)

    Explains that there are many difficulties separating scientific hope from technical reality.
    http://www.atse.org.au/index.php?sectionid=477

    Ethics

  • Stem cell therapies: a tale of caution (Medical Journal of Australia, 4 August 2003)

    Explains that much work remains to be done to turn stem cell therapy into a practical reality for degenerative diseases affecting the nervous system.
    http://www.mja.com.au/public/issues/179_03_040803/byr10862_fm-1.html

    Glossary

    dopamine. A brain neurotransmitter (a chemical that carries messages between brain cells). In people with Parkinson's disease, their dopamine-producing cells degenerate causing loss of normal muscle function.

    immune rejection. Can occur as a result of a transplant when the donor type of cell or organ is not a close enough match to the recipient type. Drugs to suppress the patient's immune system help reduce this problem. For more information see Transplant rejection (Medline Plus Medical Encyclopedia, US National Library of Medicine and the National Institutes of Health).

    insulin. A hormone produced by special cells in the pancreas. Insulin allows glucose to enter the body's cells, where it is used as an energy source. In type 1 diabetes (insulin-dependent diabetes) the body does not produce insulin, causing glucose to build up in the blood, giving high blood sugar levels. Type 1 diabetics can't make their own insulin so they must inject it every day. For more information see Type 1 diabetes (Medline Plus Medical Encyclopedia, US National Library of Medicine and the National Institutes of Health).

    mesenchymal stem cell. A type of adult stem cell found in bone marrow that gives rise to a number of different kinds of cells (eg, bone cells and fat cells). They are also known as bone marrow stromal cells. For more information see Mesenchymal stem cells (International Society for Stem Cell Research).

    placenta. A temporary organ that develops in the uterus during pregnancy. It provides nutrients for the fetus and eliminates its waste products.

    pluripotent stem cell. A stem cell able to give rise to almost all cell types in the body. There are also two other types of stem cell: totipotent and multipotent. A totipotent cell has the ability to give rise to all cell types, while multipotent cells can only differentiate into a limited range of cell types. For more information see Saving superman: A look into stem cell research (National Center for Case Study Teaching in Science, USA).

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