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Alchemy of stem cell research

If the embryonic stem cells have an unlimited selection of areas of specialization - the tissue-characterized stem cells, although they have not yet reached maturity, are similar to young professionals who have already started their careers: they still have options, but few., writes David Anderson of Caltech

As a biologist who has been researching brain stem cells for more than a decade, I find that the current debate on embryonic stem cells is increasingly disconnected from scientific reality. Embryonic stem cells are primitive cells that have extensive potential to develop into all types of cells that exist in the body - liver cells, for example, or cells that produce insulin, or nerve cells. These are very early cells, which have not yet chosen a field of specialization.

One of the arguments raised against federal funding for embryonic stem cell research is that stem cells taken from adult tissues could be used instead. Mature and less versatile cells can usually produce only the specialized cell types of the organs from which they were taken; The focus was on blood-forming stem cells, which originate from the bone marrow, because they are relatively easy to reach. Some experiments suggest that these cells have the potential to change their field of specialization in the right environment. But in most cases this is not a final conclusion.

In any case, it is one thing to say that the stem cells have the potential for something, and quite another to understand how it can be revealed and controlled. It seems that in the current discussion they forgot how difficult it is to make the stem cells do something specific.

In my laboratory at the Lipornia Institute of Technology we study neural stem cells - the stem cells that build the nervous system in the developing embryo (we work on stem cells derived from rat embryos). These are "tissue-characterized" stem cells, taken at a later stage of development than the stage where embryonic stem cells are found, taken shortly after the egg is fertilized.

If the embryonic stem cells have an unlimited selection of areas of specialization - the tissue-characterized stem cells, even though they have not yet reached maturity, are similar to young professionals who have already started their careers: they still have options, but few. For example, neural stem cells can develop into several types of nerves and glial cells (the cells that provide the electrical insulation of nerve fibers), but they cannot develop into blood or liver cells. Nevertheless, if we can understand how these cells choose between the specialization options before them, we may be able to understand how the embryonic stem cells with more potential choose their destiny.

I remember the day when one of my students informed me that he was able to discover how to reveal the potential of the neural stem cells. For years they have been in petri dishes, stubbornly refusing to reveal even a tendency to become neurotic as a result of their exposure to molecular compounds. For a long time we thought that we were doomed to produce only glial cells. You can imagine our surprise when we discovered that the miracle fertilizer, which allowed some of them to develop into nerves from which sprout axons and dendrites, similar to the branches of the bougainvillea - was not a complex mixture of sophisticated hormones, but the boring compound we used to coat the bottom of the petri dish so that the cells would stick to it.

Now we know that neural stem cells can develop into neurons or glial cells. But we still didn't know how they choose. For months we tried to force them to choose one career over the other, but they continued to produce thousands of neurons and glial cells.

One morning a student appeared in my office and modestly asked me if I wanted to see something wonderful. When I looked through his microscope I was surprised to see entire colonies of cells that had all turned into nerves - not a single glial for medicine. Through trial and error he was finally able to find a molecular signal that the neural stem cells obey, one that makes them all choose the neural career.

All this shows how difficult it is to learn to speak the language of cells. If it is so difficult to figure out how to make even a relatively educated neural stem cell become a nerve instead of a glial, imagine how difficult it is to find the way to make the more naive embryonic stem cell develop into one of the 200 characteristic cell types in the body.

However, this is still a more promising research path than trying to make mature stem cells, which exist only in certain organs, abandon their old role and develop into completely different types of cells, which we can use to cure diseases.
There is no doubt that the degree of flexibility of mature stem cells must be continued, but not at the expense of embryonic stem cell research.

My fellow embryonic stem cell researchers are making consistent and encouraging progress. But much of stem cell research is still little more than alchemy. We keep throwing things into the bubbling cauldron of petri dishes until something happens.

But the most exciting thing is that something always emerges in the end, if you have enough patience, persistence and money. In such a trial-and-error study, a larger number of researchers will enable us to more quickly discover all the signals required to make the embryonic stem cells turn into all the types of cells found in the body. Without federal funding,
Only a limited number of people will be able to work in the field of human embryonic stem cell research, and research will progress slowly. And the longer the research is delayed, the more people will die who could otherwise have been saved.

^^The writer is a professor of biology at the California Institute of Technology^^

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