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image European Research News Centre > Medecine and Health > An exceptional exception
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image image image Date published: 18/12/2001
  image An exceptional exception

 

RTD info 32

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  Stem cells are a double exception to the rule of cell specialisation - hence their interest. Not only are they able to reproduce identically (and exceptionally quickly) throughout their lives but, more importantly, they are able to differentiate to form several (sometimes in very large numbers) distinct cell types.
   
     
   

At birth, human beings are made up of approximately 100 000 billion cells belonging to around 200 different categories (nerve, muscle, secretory, sense cells, etc.). Each of these groups is able to effect a number of very specialised tasks. As the body develops, the cells multiply by a process of division: when tissues deteriorate or wear out, it is generally the cells in the vicinity of the damaged zone which proliferate and try to compensate for the losses. Over time, however, this regenerative ability is progressively lost and ultimately disappears in many vital organs. Also, when the cells divide they are only able to produce daughter cells which are similar to themselves.

This is why the discovery of the role and properties of stem cells (known as multipotent when they can form several types of cells and pluripotent when they can form all of them)(1) brings new and exciting prospects. Tissues formed from cells so specialised that they are virtually unable to be renewed could - if damaged - be 'reconstructed' through the addition of a sufficient number of stem cells. In any event, that is the underlying idea of what it is hoped is a new field of medicine in the making: regenerative medicine.

From ideas to practice

In practice, however, things are not that simple, in particular because not all stem cells are the same. Their therapeutic value depends on a number of factors: accessibility, ability to proliferate and to differentiate, etc. The most promising are embryonic stem cells (ESCs). These are obtained from embryos at the blastula stage (hence the name blastocytes), when the embryos are about ten days old and comprise approximately one thousand cells. Some of them, although not totipotent (i.e. able to regenerate a complete human being) are able to form any kind of cell if placed under the right conditions.

Obtaining this material with extraordinary properties means destroying a human embryo, even if it is created in vitro and is made up of just a few hundred cells. This clearly poses ethical problems (see Facing omnipresent ethical problems) which have caused the scientific community to seek alternative products.

Various tissues rich in stem cells, taken from aborted foetuses, raise issues scarcely less sensitive. This is why research financed by the European Commission - leaving aside work on umbilical cord blood, a waste product usually destroyed at birth - is concentrating on adult stem cells which are present in virtually all our bodies.

The adult stem cell solution

Where are such stem cells found? Since the search really got under way, around 1999, they have been found concealed in the most diverse areas of the body. There are some - albeit not many - in the brain, and also in the bone marrow, blood, skin, and blood vessel walls. But it seems that these adult cells are more difficult to cultivate, are slower to reproduce and are only able to generate a limited number of tissues, when compared to embryonic cells. Or at least that was the belief until very recently. The fact is, we are no longer very certain about very much in this field as so much of what seems to have been established just two years ago has been overturned in recent months.

When placed in culture environments, neuronal stem cells have not only been able to form neurons but also cardiac, intestinal and renal cells. Similarly, haematopoietic stem cells (destined to form blood) have proved able to produce hepatic, renal, muscular or neuronal tissue. What is more - and until recently this would have been judged the ultimate 'heresy' - the American Academy of Sciences has reported that 'there are rare but well-documented examples of differentiated stem cells in developing mammals which change destiny and transdifferentiate into another cell type'. It therefore seems increasingly probable that by changing the environment in which cells live it is possible to influence their future role. Researchers are now looking for molecules (growth factors) which make it possible to 'instruct' a cell to evolve into what is required.

A revolutionary therapeutic tool

If these techniques could be mastered, they would certainly bring previously unimagined possibilities. One of the major problems of transplants, for example, is that the patient rejects the transplanted tissue as the body identifies it as coming from another person. If, on the other hand, the patient's own stem cells were used to reconstitute the damaged tissue, such problems of rejection would disappear. This, in turn, has led to many discussions on the subject of 'therapeutic cloning' in which an ovule (ovocyte) is first extracted so that the nucleus of a cell taken from a patient can be inserted into it before the egg is then allowed to develop to the blastula stage. The embryonic stem cells thus obtained would, in theory, be able to reconstitute any patient tissue whatsoever.

Stem cells could also prove to be the elusive tool needed for successful gene therapy. Scientists are known to be trying to introduce genetically modified cells into the tissue of patients to correct certain malfunctionings. It is conceivable that stem cells could be taken from a patient, supplemented with one or more genes (to restore a lost biological function, for example) then multiplied and reintroduced into the affected tissue.

Caution

As always when a new field of research opens up, we must be prepared for all kinds of setbacks. Margaret Goodell, author of a key article on adult stem cells in 1999, recently told the journal Nature that: 'Science does not at present justify what some people are saying, namely that adult stem cells can do everything.' The truth is that at the present stage the exceptional results obtained on mice and sheep are sometimes impossible to reproduce in man. Molecules which appear very effective in the test tube may have no effect at all when introduced into a patient's tissue, or alternatively may be accompanied by serious side effects. The multiplication techniques developed to proliferate stem cells are able to achieve their purpose, but they also have the unexpected effect of preventing any subsequent differentiation. Also, a success in one case does not mean that it can be reliably reproduced, or that all the stages can be controlled. What is more, the extraordinary dynamism of stem cells brings with it the fear that, under certain conditions, they could produce tumour growth.

Biologists therefore urge caution. There must be no repeat of the adverse experience of gene therapy when all sorts of wonders were promised before it was realised that it will be a long time before effective treatment becomes available. 'It is no doubt the beginning of a new era, but at present there remain whole areas in which very little is understood. Above all we must persevere with our research,' is how Eliane Gluckmann, coordinator of the Eurocord project (see European projects) sums up the situation. Hence the legitimacy of caution - not that it is likely to dampen current passionate curiosity.

(1) As opposed to totipotent, meaning able to re-form a new embryo.
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Image of a remarkably homogenous human neural stem cell obtained by cloning. Each cell (cell nucleus stained blue) expresses the neural stem cell filamentous marker, nestin (in green).Research carried out as part of the Ectins project.

Image of a remarkably homogenous human neural stem cell obtained by cloning. Each cell (cell nucleus stained blue) expresses the neural stem cell filamentous marker, nestin (in green).
Research carried out as part of the Ectins project.

 

Stem cells conference website

 

 


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