Liver from the spleen
The spleen was turned into a liver inside a live mouse
Polina Loseva, N+1
Chinese biologists have developed a method that allows you to turn one organ into another, that is, to grow a liver on the frame of the spleen. To do this, the original spleen needed to be treated with a tumor extract – to suppress the immune response and cause the growth of intercellular matter. After that, liver cells were planted in it, which took root inside and formed structures characteristic of the liver. The transformed spleen turned out to be a good replacement – at least the animals survived after the original liver was almost completely removed. The work was published in the journal Science Advances (Wang et al., Transforming the spleen into a liver-like organ in vivo).
The easiest way to cope with liver failure is to transplant a new one to the patient. However, it is not always possible to find a donor in time, and the organ itself after transplantation may not take root or not earn in full. And the main obstacle here is in the vessels: the donor organ must dock with different vessels and ducts coming out of it, otherwise it will be useless. The same problem arises with artificial organs – attempts to grow them in vitro are broken by the need to completely restore the vascular bed inside the organ.
A group of biologists led by Lei Dong from Nanjing University has proposed an alternative approach to the problem: to grow a new organ right inside the patient's body. And the vascular framework, according to their idea, can be borrowed from some other organ that is not vital. In the case of the liver, the spleen could become such an organ: it is quite large, well supplied with blood, but it is not critical for life. People with a removed spleen do not suffer from serious diseases, so it could be sacrificed in favor of the liver.
To begin with, the researchers moved the spleen of experimental animals under the skin – this makes it easier to track its condition. They checked that after moving the organ retained its size and morphology, and its cells produced a standard set of spleen proteins.
After that, the first stage of the transformation of the spleen began. In order for a full-fledged liver to grow in it, it was necessary to prepare it: reduce the activity of the immune system and allow newly arrived cells to divide. To do this, the authors decided to treat the spleen with an extract of a mouse tumor. They tested the effects of four extracts: melanoma, sarcoma, liver and breast cancer. It turned out that sarcoma extract most strongly increases the expression of collagen (a protein of intercellular substance necessary for the construction of the liver) and anti-inflammatory interleukin-10 in the spleen. Therefore, the researchers continued to work with this extract.
Biologists have found that under the action of sarcoma extract, the spleen under the mouse skin grows strongly and begins to weigh almost twice as much as usual. The expression of 4800 genes changes in it, there are fewer clusters of lymphocytes and more intercellular matter. At the same time, this transformation, according to the authors of the work, did not affect the health of the mice themselves and the work of other organs in any way.
At the second stage of transformation, the spleen had to be populated with liver cells. The researchers tested four types of cells: the mouse's own liver cells, the liver cells of another mouse, human liver cells, and liver cells grown from reprogrammed human cells. All of them took root in the spleen after treatment with tumor extract and remained there for two weeks after the extract was stopped being injected (and the liver's own cells remained in the spleen even longer). At the same time, mouse liver cells were able to occupy a significant part of the organ and form structures characteristic of the liver there, including bile ducts.
The transformed mouse spleen (left) is much larger than the normal one (right).
Finally, the authors of the work checked to what extent the transformed spleen performs the functions of the liver. It turned out that it synthesizes fats, stores glycogen and produces blood proteins, as the liver should do. Moreover, when 90 percent of the real liver was removed from such animals, they all survived, while none of the control group (those who had cells injected into an unprepared spleen or, conversely, prepared it, but did not inject cells) survived liver removal.
Thus, the researchers found out that from the spleen, if properly prepared, you can get a good liver replacement. And this procedure does not cause serious side effects – at least in mice. Nevertheless, the authors of the work note that the transformed spleen has an important difference from the liver – the source of blood. The liver receives blood through the portal vein from the intestine, therefore, signaling substances isolated by the intestinal wall may be present in it, and the oxygen concentration is lower. At the next stage of the work, it is important to check that the absence of these signals and an unusually high level of oxygen in the blood does not destroy liver cells in the new place of residence.
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