Science: How to get blood out of a bone...

The potential for transforming human cells sets Lewis Wolpert's pulse racing, in this, the first of his new columns

WOW! IT IS very rare that I have such a strong reaction to a scientific paper, a real surprise and a sense of astonishment. Most papers in the journals add to the body of knowledge and, while they can be very interesting, excitement is rare. The last time I had such a reaction was over 10 years ago, when I first saw pictures of the zebra-like stripes of gene expression in the early fruit-fly embryo that foreshadowed the formation of the fly's body segments.

The new work comes from Italy and shows how cells in the brain are much more clever and versatile than anyone could have imagined.

During development of our brain, and that of all vertebrates, there is a layer of cells lining the wall of the tube that will give rise to the brain that gives rise to all the nerve cells, neurons, of the brain . These are stem cells. When they divide into two daughter cells, the innermost daughter cell becomes a neuron and migrates away from the wall. The other daughter cell remains attached to the wall and becomes now a mother cell as the process is repeated, and again the inner daughter becomes a neuron. Only recently has evidence been provided which shows that, even in the adult brain, there are still stem cells that can divide to give rise to neurons.

This has very important implications, as nerve cell themselves cannot divide to give more nerve cells, but can only come from stem cells and these were thought to disappear when growth and development were completed. There is thus in the adult brain the capacity to make new nerve cells, and so repair and replace nerve cells that may be lost due to damage or disease processes.

There were also a few reports that things were even more remarkable, as muscle cells were observed in the brain and were quite common in a particular type of brain tumour. But muscle cells have a quite different origin from that of nerve cells. They come from a region of the embryo thought to be as different from that from which nerve cells come as a Sanskrit sentence is from one in English. Yet some cell biologists began to speculate that brain stem cells might have a greater potentiality for development than anyone had thought possible .

They therefore began to grow stem cells from the brains of mice. They did this by putting the cells in a dish with the right culture medium, where they multiplied. They then wondered if these cells could give rise to blood-forming cells that have an origin similar to that of muscle. Blood in all vertebrates comes from stem cells in, for example, the bone marrow. Stem cells there divide and give rise to all our red and white blood cells and are very active, as our red blood cells have only a life of a few weeks. If the division of these stem cells is blocked, by for example, X-irradiation, blood cell formation ceases with very serious consequences. But it is possible to rescue the situation by injecting stem cells from another animal. With a high-risk experiment - that is, with the chance of success being very low - the researchers injected the brain stem cells into the mice that had been irradiated to see if the brain stem cells could populate the bone marrow and, in their new environment, be persuaded to make blood cells. The mice did very well and, five months later, they had unequivocal evidence - the mice blood cells had come from the neural stem cells that they had injected. They were sure because the cells they had injected carried a molecular marker that made them distinguishable from those of the mouse into whom they had been injected.

No one yet knows how the cells in the bone marrow instructed the neural stem cells to make blood cells. It is totally unexpected that signals exist which can transform one cell type into another - English into Sanskrit .

But it opens up many exciting possibilities to manipulate stem cells recently isolated from early human embryos. These cells were trumpeted as being the answer to various tissue replacement procedures, from heart muscle to insulin-producing cells and liver. I suspected there was more hype than hope, but this new work suggests I was rather pessimistic.

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