Chinese biologists have developed a method that allows you to turn one organ into another, that is, grow a liver on the spleen frame. To do this, the original spleen needed to be treated with a tumor extract - in order to suppress the immune response and cause the growth of intercellular substance. After that, liver cells were planted in it, which took root inside and formed liver-characteristic structures. The transformed spleen was a good substitute - at least the animals survived after the original liver was removed almost completely. The work was published in the journal Science Advances..

The easiest way to deal with liver failure is to transplant a new patient. However, it is far from always possible to find a donor on time, and even the organ itself after transplantation may not take root or not fully earn. And the main obstacle here is in the vessels: the donor organ must dock with different vessels and ducts leaving it, otherwise it will be useless. The same problem arises with artificial organs - attempts to grow them in vitro break up about the need to restore the completely vascular bed inside the organ.

A group of biologists led by Lei Dong of 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, is well supplied with blood, but is not critical for life. People with a removed spleen do not suffer from serious illnesses, so they could donate it to the liver..

To begin with, the researchers moved the spleen of experimental animals under the skin - it's 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 this, the first stage of spleen transformation began.. In order for a full-fledged liver to grow in it, it was necessary to prepare it: reduce the activity of immunity and allow newly arrived cells to share. For this, the authors decided to treat the spleen with a mouse tumor extract. 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 (the protein of the intercellular substance necessary for building the liver) and anti-inflammatory interleukin-10 in the spleen. Therefore, the researchers further worked with this extract..

Biologists found that under the action of the extract of the sarcoma of the spleen under the skin of the mouse grows strongly and begins to weigh almost two times more than usual. In it, the expression of 4800 genes changes, there are less accumulations of lymphocytes and more intercellular substance. Moreover, according to the authors of the work, this transformation did not affect the health of the mice themselves and the work of other organs.

At the second stage of transformation, the spleen had to be populated with liver cells. Researchers tested four types of cells: mouse’s own liver cells, another mouse’s liver cells, human liver cells, and liver cells grown from reprogrammed human cells. All of them took root in the spleen after treatment with the tumor extract and remained there for two weeks after the extract was no longer administered (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, including bile ducts, there.

The transformed mouse spleen (left) is much larger than usual (right).

Finally, the authors of the work checked how transformed the spleen performs liver functions.. It turned out that it synthesizes fats, stores glycogen and produces blood proteins, as it should be done by the liver. Moreover, when 90 percent of the real liver was removed from such animals, they all survived, while no one survived the removal from the control group (those who injected cells into an unprepared spleen or, on the contrary, prepared it but did not inject cells).

Thus, the researchers found that from the spleen, if you prepare properly, you can get a good liver replacement. And this procedure does not cause serious side effects - at least in mice. However, the authors 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 secreted by the intestinal wall may be present in it, and the oxygen concentration is lower. At the next stage of work, it is important to verify that the absence of these signals and the unusually high level of oxygen in the blood does not destroy liver cells in a new place of residence.

We already wrote about other approaches to repairing the liver - for example, you can temporarily patch it with stem cells while doctors are looking for a donor, or even collect a new liver from scratch in separate cells. All these approaches have not yet left the rank of pilot, but in the future they may turn out to be safer than the usual transplantation.. For example, we once told the story of an HIV-infected patient who was given a second HIV strain by a kidney transplant.

Polina Loseva https: // nplus1. com /.

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