03 June 2020

A rat with a human liver

A rat was transplanted with a human mini-liver grown from stem cells

She successfully took root and began diligently purifying the rodent's blood from toxins

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For the first time, scientists have grown a full-fledged analogue of a human liver from stem cells and successfully implanted it into a rat's body. The organ was successfully able to purify the blood of rodents and produce bile. A description of the work was published by the scientific journal Cell Reports (Takeishi et al., Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells).

"Our long–term goal is to learn how to grow artificial organs that can replace donor organs. In the near future, the organoids we have created may become a "bridge" to transplantation. For example, in case of acute liver failure, it will be possible not to transplant the liver, but to remove the load from the damaged organ," commented one of its authors, associate professor at the University of Pittsburgh (USA) Alejandro Soto-Gutierrez.

Over the past ten years, scientists have repeatedly tried to create artificial liver analogues using embryonic or stem cell cultures. Japanese researchers completed the first such experiments back in 2012: then they reproduced some of the liver functions of mice on artificially grown organoids of small size.

Subsequently, biologists created and tested in practice several other variants of such an "artificial liver", gradually increasing its size and functionality. All these experiments were conducted on animal cell cultures, which is why the researchers were not sure that something similar could be obtained using human reprogrammed stem cells.

Artificial human liver

Soto-Gutierrez and his colleagues have taken the first step towards solving this problem. They grew a complete replacement for the liver from stem cells obtained by reprogramming connective tissue cells from the skin of several volunteers. Using various sets of nutrients, hormones, signaling molecules and other substances, scientists have transformed them into three key types of liver cells – hepatocytes, cholangiocytes and endothelial cells. The former are involved in the purification of blood from protein "garbage" and toxins, as well as in the production of urea, the latter are responsible for the production of bile, and the third – for the removal of waste products from the liver.

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Using cultures of "blanks" of these cells, Soto-Gutierrez and his team grew miniature likenesses of a human liver. Then the researchers "seeded" them with special protein scaffolds. Scientists obtained them by cleaning liver fragments from the cells present in them. Thanks to this, Soto-Gutierrez and his colleagues received a full-fledged liver tissue permeated with blood vessels and bile ducts.

After spending a total of a month growing this mini-liver, biologists implanted several copies of it into the bodies of rats. As subsequent observations showed, the artificial organ took root and began to produce bile, purify the blood from toxins and convert excess nitrogen compounds into urea.

While such miniature likenesses of the liver are not ready for transplantation into the human body. However, scientists suggest that in the very near future they will be able to make such artificial organs safe for people. Thanks to this, it will be possible to save the lives of many patients who need an immediate liver transplant, but there are no suitable donors.

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