Nikolay Dyatlov: liver from a test tube

Nikolai Dyatlov Source: Nature.com

In the magazine, SENCE for July 20, 2012 published the news agitating medical community: Japanese scientists closely approached the creation of an artificial, grown “in a test tube” of the liver.

The biologist-researcher of stem cells Takanori Takoeba from the University of Yokogama (Japan) presented the results of his research at the annual meeting of the International Society for Studies in the Field of Stem cells in Yokogam. Using pluripotent (that is, able to realize several options for further development) stem cells obtained from human skin cells, Takebies and his colleagues were able to grow “in a tube” of tissues that are very similar to the human liver, containing the most important liver cells - hepatocytes.

At the next stage, scientists added two more types of cells to the drug: endothelial cells of the umbilical cord, of which the walls of the vessels consist, and mesenchymal cells from the bone marrow, which can turn into bones, cartilage or fat. Two days later, the cells formed in the volumetric, five -millimeter formation - the embryo of the future liver.

Although the development of the embryo largely repeats the development of the organ in the embryo, this is not a full -functional liver. There are no bile paths in it, and hepatocytes do not form neat “beams”, as in a real liver. However, there are active blood vessels in the bud, and they function when transplanting the “liver” under the skin of experimental mice, and it can transform some drugs that people can metabolized and cannot mouse. It took more than a year and hundreds of trials to achieve such results, Takebies, since the most difficult thing was to correctly calculate the time of introduction of the second and third types of cells.
It is too early to talk about whether it will be possible to grow a whole liver. The liver transplants require the most severe cases, and at the same time there is a huge toxic load on the transplanted organ - it is not clear whether an artificial liver can cope with it. But the most important thing is that it should maintain stable dimensions, not degraded, but also not to continue to grow - both options can be deadly for the recipient.

However, scientists are sure that the benefits of their creation will still be: artificial embryos of the liver can be used to test medicines for hepatotoxicity.

Typically, such tests are carried out on mice, which transplant the cells of the human liver, but they are absorbed by the body of the rodent in a few days, and the liver “from a tube” can function longer. Now the researchers are faced with the task of increasing the amount of albumins produced by the embryo - the most important protein for the work of the liver - and “grow” the bile ducts.

Another Japanese scientist, Sasai Yoshiki from the Center for Development Biology in Kobe (Japan), achieved no less stunning results on the basis of stem cells. At the same conference, he spoke about his successes in growing an eye glass - the predecessor of the human eye. This is a three -dimensional cellular structure with a size of 550 micrometers, consisting of several layers of mesh cells, including photoreceptor.

The most amazing that the voluminous structure of the eye glass was formed from stem cells on its own, just as it happens in the human embryo.

At first, predecessor cells form a ball of epithelial cells, which is then inflated into the eye bubble, and he, in turn, “folds” into itself, forming a “cup”, on the outer side of which there is an epithelium of the retina, and on the internal-photoreceptors, bipolar and ganglionic cells. But it is no less important that there are no initial stem cells in it - that is, they all “specialized”, and there is no danger that unwanted growth will continue in the artificial organ.

This technology can theoretically allow to grow a retina available for transplanting in eye diseases. It may even work to “cook” it in advance and freeze it. But theoretical consequences from this experience are no less important. Sasai has already managed to successfully grow the eye glass from the stem cells of the mouse, and it turned out that when using human cells, the eye glass is twice as large in diameter and ten times more in volume. Since both organs were grown “in a test tube”, such a difference in size suggests that, at least, the size of the organ is not set “from the outside”, but is the immanent property of the cell itself. This opens up great prospects for growing organs as a whole.

True, other scientists still have not been able to repeat the successes of Sasai. Probably, it will take years before it is possible to grow full -functional organs. But this does not mean that studies of stem cells are exclusively long -term “investments”. In fact, they have their real fruits now.

The ten -year -old girl from Sweden became the first person in the world to be transplanted by a large blood vessel grown from her own stem cells.

The girl had a clogging of a vein in the liver, and in order to avoid complications from someone else's transplant, they decided to grow Vienna from her own cells. Of course, this was not done “from scratch”, since the cultivation of volumetric cellular structures is still very far from perfection. As a “construction forests”, the vein of a recently deceased donor was taken, all living cells were removed from it and only the protein structure was left. Then, the venous walls were increased on this frame using cells from the girl’s spinal cord. Since there were no other people's cells in Vienna, it took root, and it was not required to use immunode drugs, as in the case of transplanting a donor organ. A year later, the girl was performed an additional operation, and now she feels good and stably grows.

Studies of stem cells are one of the most promising areas of medicine. Their potential is huge, since in theory of them you can grow any type of cells necessary for a person, and they will not be rejected by the recipient, as they are his own. Successful cultivation of organs from stem cells can completely change the situation with queues for transplanting surgery and at the same time save patients from problems with the rejection of the organ of the immune system. This, in turn, can significantly improve the quality of life of older people who often encounter diseases requiring the use of such technologies.

But before it becomes everyday practice, scientists will have to solve many complex tasks: at least, learn to grow complex three -dimensional cellular structures without the help of “building forests” from other people's cells and control cells to avoid cancer.