12 September 2013

Reprogramming of cells in a living organism: the first pancake

Reprogrammed mouse
Biologists reprogrammed cells not in culture, but directly in a live mousePolina Rozentsvet, <url>

Spanish biologists have turned mature cells into stem cells right in the body of an adult mouse.

The cells obtained in this way have unprecedented development potential.

Embryonic stem cells, capable of giving rise to any of the hundreds of cell types that make up the adult body, attract the close attention of specialists in the field of transplantology and regenerative medicine. With the help of these cells, it would be possible to treat such serious ailments as diabetes, Alzheimer's and Parkinson's diseases. But embryonic stem cells exist only in the first few days of embryonic development, there are none in the adult body, and there can be no question of putting the production of embryos on stream. Until now, cells with similar properties have been obtained in the laboratory, under cell culture conditions.

Specialists of the Spanish National Cancer Research Center under the leadership of Manuel Serrano reprogrammed mature cells directly in the body of an adult mouse for the first time, and they acquired unique properties inherent only in stem cells in the first hours of embryo development. It was not possible to obtain cells with such characteristics on nutrient media.

In 2006, Japanese scientist Shinya Yamanaka, working with mouse cell culture, reprogrammed mature cells in such a way that they lost differentiation and were able to transform into cells of different tissues under certain influence. The scientist found that reprogramming requires the products of four genes – Oct4, Sox2, Klf4 and c-Myc. The resulting cells were called induced pluripotent stem cells (iPSCs). Yamanaki's research, for which he received the 2012 Nobel Prize in Medicine, opened new horizons for regenerative medicine.

The Spanish researchers did not work with cell culture, but with live mice. They obtained transgenic animals with sequences of all four genes involved in cell reprogramming. The genes were inoperable and activated in response to the drug doxycycline, which was added to adult mice in drinking water. Teratomas are formed in mice "activated" in this way – this is a special kind of tumors that arise from improperly developing embryonic cells. Most teratomas are a "mixture" of different tissues: connective, epithelial, muscular, nervous and others. In "activated" mice, teratomas were found in almost all tissues and organs: kidneys, liver and pancreas, in the intestines, stomach, adipose tissue and inside the skull, on the serous membranes of the abdominal and thoracic cavities. In the composition of tumors there are even trophoblast cells – a structure that is not part of the embryo, but is necessary for its nutrition.

The formation of teratomas on the formed organs indicates that the cells of these organs have lost differentiation and changed the development program directly in living mice. Cells that have lost their specialization circulate in the bloodstream and synthesize proteins characteristic of embryonic stem cells at an early stage of embryo development.

Pluripotent cells from "activated" mice can be isolated and cultured on nutrient media. If they are injected under the skin of ordinary mice, embryo-like structures are formed in their abdominal and thoracic cavities, which contain all three germ leaves and trophoblast cells.

"Yamanaka cells" – iPSCs – also cause the formation of teratomas if they are injected under the skin of mice. But such teratomas contain only embryonic tissues and never trophoblast. Therefore, Spanish researchers say that the possibilities of pluripotent cells obtained by them in live mice are greater than the potential of iPSCs grown in culture.

The reprogrammed cells that emerged in living mice have the characteristics of embryonic cells at the 72-hour stage of human embryo development, when it consists of only 16 cells. Cells with such capabilities have not yet learned to receive on nutrient media.

So, the specialists of the Spanish National Cancer Research Center have shown that in an adult body it is possible to obtain embryonic stem cells with hitherto inaccessible potential.

The capabilities of these cells have yet to be studied. In addition, researchers will have to develop methods that would allow reprogramming cells in a certain place and in the right direction. And, of course, it must be proved that the phenomenon described in mice also exists in humans. Scientists emphasize that the practical use of their discovery in medicine is still very far away.

Portal "Eternal youth" http://vechnayamolodost.ru12.09.2013

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