07 October 2008

An embryo in every cell

Pyotr Smirnov, "Newspaper.Ru»

It is now possible to transform a cell of one type into another directly. Created for the sake of demonstrating the method, the virus turns the sources of digestive juices into "insulin factories". The return of cells to the embryonic pluripotent state on this path is an extra hook.

Ask even the most astute sage these days: "How will medicine develop in the coming years and decades?" – and you are unlikely to get an unambiguous answer. Now there are at least two "new" directions showing good results in the treatment of incurable diseases that have recently been treated. These are genetic engineering and cell transplantology.

The two fashionable branches of medical science differ in the object of their application, but this does not interfere at all with the mutual penetration of ideas, techniques and tricks. Moreover, the branches support each other, and then one, then the second invariably uses the achievements of the other as a tool in achieving their own goals.

Having felt the power, but not yet understanding the boundaries of the two fields of medical science, humanity began to search for a place to apply their achievements and divide spheres of influence in medical practice. While genetic engineering has secured the fight against hereditary diseases, and the application of cell transplantology remains regenerative medicine that restores acquired defects of organs and tissues of our body.

It so happened that diabetes mellitus and insulin closely related to it very often became a real guiding star for pioneer scientists. The first decoded protein, the first recombinant protein and many other physiological and biological terms with the definition of "first" are associated with this problem.

This time we are talking about the first transformation of adult cells from one type directly into another type – moreover, in a living organism.

And even though it has not yet been possible to create a little brain from bone tissue, the achievement of American doctors is no less impressive. They were able to turn exocrine cells of the pancreas into insulin-secreting beta cells.

The pancreas itself is unique: it performs both an endocrine function, secreting the hormone insulin into the blood, and an exocrine one, secreting digestive enzymes into the lumen of the duodenum.

As in most glands, a separate cell type is responsible for the synthesis of each substance. Beta cells synthesizing insulin are assembled into small conglomerates, called Langerhans islands. And most of the pancreas is occupied by exocrine cells that secrete trypsin into small ducts that, when combined, "flow" into the duodenum.

Both these and other cells are highly specialized and, as a result, highly differentiated, that is, they are at the very end of the differentiation line leading from the once merged egg and sperm to every cell of our body. Neither beta cells nor exocrine cells of the pancreas are practically unable to divide, let alone any transformations into other types of cells. At least, that's what it used to be.

For biologists who learned last year how to turn adult skin fibroblasts into embryonic stem cells, any other focus seems less difficult.

However, the work on turning digestive enzyme sources into "insulin factories", the results of which Douglas Melton and his colleagues from the Harvard Stem Cell Research Institute and the Howard Hughes Medical Institute published in Nature, stands out even against this background.

And by its methodology, and the absence of the notorious stem cells in the recipe for success. And it can also be noted that Melton and his colleagues finished work on their project six months before the November accomplishments.

Attempts to grow beta cells from stem cells, and then transplant them into the body were made and even were quite effective. Melton went the other way. He and his staff decided to do without stem cells and additional in vitro manipulations. Scientists have managed to reprogram adult exocrine cells using transcription factors – molecules that regulate the reading of genetic information.

But Melton's main achievement is that this reprogramming was carried out in a living organism – more precisely, in the pancreas of a mouse.

Scientists have selected nine factors characteristic of embryonic progenitor cells that eventually turn into beta cells. The necessary sequences were inserted into the middle of the neutralized adenovirus, after which mice were "infected" with this virus using a conventional injection. The virus delivered nine code sequences to the right cells and forced them to synthesize the corresponding molecule codes. Later it even became clear that the list of factors could be reduced from nine to three names: Ngn3, Pdx1 and Mafa.

Within a month, new beta cells appeared in the mouse pancreas, organizing like the islands mentioned, only in much smaller quantities. These newly formed cells, in a good sense of the word, not only structurally did not differ from typical beta cells, but were also fully functional - they secreted insulin. In addition, they independently stimulated small vessels to grow, providing themselves with a good blood supply and a place to "dump" the hormone.

Scientists even proved that the process of "transformation" took place without transitional stages, that is, beta cells immediately turned out of exocrine cells, without intermediate formation of progenitor cells.

Perhaps because of this, new cells practically did not divide: in the pancreas of rodents, only 3% of them were divided during 10 days of observation. While the "old" did it four times more often (13%).

The latter circumstance, which at first glance detracts from the achievement of scientists, actually brings the practical implementation of the methodology closer. The slower (in a statistical sense) the division, the easier it is to dose the effect of genetic intervention. In addition, the less likely the appearance of tumors is, and this is the main danger that lies in wait for the "new medicine" on the way to patients.


Portal "Eternal youth" http://www.vechnayamolodost.ru07.10.2008

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