Stem cell biology

Stem cell biology

An article written by Professor Sir Ian Wilmut FRS, Professor Ian Chambers and Dr Gareth Sullivan.

Innovative use of stem cells will provide new treatments for human diseases.  These include the first drugs able to provide effective treatment for degenerative conditions (such as Parkinson’s and motor neurone disease) and the transfer of cells to replace those that have died or ceased to function normally. 

Professor Sir Ian Wilmut FRS talks about stem cell biology. (4 mins, requires Flash Player).

Research to develop methods of "reprogramming" cells directly from one state to another has been ongoing since the early work on frogs by Professor Sir John Gurdon FRS, which first demonstrated that the fate of cells is far more adaptable than had previously been imagined. The cloning of Dolly the sheep further demonstrated that such reprogramming strategies could result in the successful development of adult mammals. Revolutionary opportunities are now being offered by the emerging technique which enables us to transform a patient’s skin cells into a different tissue for use in research or therapy.

    Professor Deepak Srivastava on stem cells and heart disease (2 mins).
  • Listen here.

Stem cells are unique in that, when they divide, they are able either to form daughter cells like themselves or to form different types of cells.  Stem cells have been identified at many different stages of development from the early embryo through to the tissues of an adult.  Those recovered from early embryos can multiply many times in the laboratory and are able to form the specialised cells that make up all the tissues of an adult animal. These types of cells are known as pluripotent cells and are extraordinarily useful in research. In contrast, stem cells found in adult tissue have a limited ability to multiply and can only form different cell types that are present in that tissue. 

‘Dolly the sheep’, who was cloned by Professor Sir Ian Wilmut FRS and colleagues at the Roslin Institute (credit: Roslin Institute).

These two were the only sources of stem cell until 2005, when a groundbreaking experiment by Japanese researchers Kazutoshi Takahashi and Shinya Yamanaka established a procedure which makes it possible to take adult cells and change them so that they become very similar to embryo stem cells.  This new cell is known as an "induced pluripotent stem cell".

The characteristics of cells are controlled by a network of proteins that regulate the expression of genes. Yamanaka demonstrated that by the introduction of just four selected "transcription factors" it is possible to change cells to pluripotent cells.  The initial process had a number of limitations - it was slow, only able to change a small proportion of cells, and involved potentially mutagenic retroviruses and known oncogenes. 

    Professor Sir Ian Wilmut FRS on why stem cells are important (4 mins).
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Subsequent research identified a number of additional transcription factors that promote the change.  Technical changes have also been developed which either avoid the use of tumour forming genes or ensure their safe removal from the treated cell.  A similar approach has been used by Marius Wernig to produce nerve cells from the skin, where the transcription factors introduced are believed to be responsible for the normal function of neurones. Despite these advances a great deal still remains to be learned about the methods for changing cells in this way before they can be considered for use in cell therapy. 

The ability to produce induced pluripotent cells from patients with inherited diseases makes it possible to study in the laboratory cells equivalent to those from the affected tissue of a patient at an early stage of disease development. This approach is being used in research into different conditions, including motor neurone disease, blindness, Parkinson’s disease, muscular dystrophy, Huntington’s disease and heart failure.

Robert Hooke’s drawing showing the structure of cork. He used the word ‘cell’ for the first time when describing this image. From the Royal Society archives.

Induced pluripotent stem (iPS) cells from selected donors may one day form a library of cell lines that can be used for cell therapy, particularly to treat degenerative and genetic diseases. When cells from another person are transferred into a patient it is essential to ensure that immune rejection does not lead to the death of the transplanted cells.  Craig Taylor has estimated that a relatively small number of carefully selected cell lines may be able to provide an acceptable cell therapy for the great majority of patients.  Such a library could be established once safe and reproducible methods for production of iPS cells become routine, providing a resource for the general public.

In addition to the biological challenges, provision of cell therapy does not fit readily within pharmaceutical or private healthcare companies, or state health care organisations.  For instance, biologists are striving to produce cells for the treatment of diabetes.  At present type 1 diabetics are treated by injections of insulin which has significant limitations - it is expensive in the long-term and, over a period of years, diabetics may become blind or suffer kidney failure. If appropriate cells were transplanted into the patient, many of these clinical limitations could be avoided.  However, the development and delivery of this treatment would involve considerable financial outlay and efforts would need to be made to ensure that the costs of treatment remained comparable to that of long-term insulin treatment.

Clearly, stem cells hold great promise for improving human health. However, a number of hurdles, both scientific and logistical, will need to be surmounted before cell therapy could be applied on a large scale.

Banner image: Derived neuron (credit: Sally Lowell).

Discussion meeting

This article is based on the discussion meeting 'What next for stem cell biology?' which was held on 18-19 October 2010.

From the Royal Society's archives

When Robert Hooke FRS coined the term “cell” in his pioneering 1664 work Micrographia, he was viewing sections of cork at what was then an unprecedentedly high magnification. Later microscopists recognised structure within plant cells, with Robert Brown FRS naming the nucleus in the early nineteenth century.

However, the first revolution in cell biology did not occur until the 1850s, with the insight of Theodor Schwann and Matthias Schleiden that cells were ubiquitous in living things. It was a short step from there to the realisation (by Robert Remak and Rudolph Virchow) that cells originated only from other cells. The centuries-old belief in spontaneous generation – the idea that living tissue could appear spontaneously from non-living matter – could finally be laid to rest.

Virchow shared with Albert von Kolliker the distinction of being awarded the Royal Society’s Copley Medal, the world’s oldest scientific prize. Kolliker’s contributions to cell biology were extensive, including the discovery of mitochondria (the cell’s energy generator). These researchers laid the foundations of an entirely new way of looking at life.

In the early 20th century, Hans Spemann began looking at how life itself begins through his ingenious experiments on developing animal embryos. Spemann famously disproved August Weismann's theory that cells lose genetic information with each division and in 1938 he proposed a ”fantastical experiment”1 – cloning organisms via the transfer of cell nuclei. He was the first person to suggest that it might be possible to produce an embryo in this way.

While the technological limitations of the period meant that Spemann’s ideas remained “fantastical” in his own lifetime, recent innovations in this area have already led us beyond Spemann’s fantastical experiment. Early cell biologists such as Hooke and Schwann could hardly have dreamed of the great advances that the latest biological revolution is likely to usher in.

[1] H. Spemann (1938), Embryonic Development and Induction, Yale University Press, New Haven