Friday, April 1, 2011


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. 

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.

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. 

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. 

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.

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.


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Publisher and/or Author and/or Managing Editor:__Andres Agostini ─ @Futuretronium at Twitter! Futuretronium Book at http://3.ly/rECc