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Scientists grow 'tiny livers' from human stem cells

“Tiny functioning human livers have been grown from stem cells in the laboratory,” BBC News reports.

This story is based on a study that used stem cells generated from adult human cells to grow a tiny “bud” of liver cells with its own blood vessels. Scientists successfully did this in the lab and found that the liver bud joined up with a mouse’s blood system when it was transplanted. Once this happened, the transplanted liver bud could also perform some of the functions that a normal liver does, like breaking down drug molecules.

The human liver is a large organ with many essential functions and, while resilient, once it has received too much damage it can fail. For example, a leading cause of liver failure is prolonged alcohol abuse. Once liver failure occurs, the only current treatment option is a liver transplant. But the demand for donated livers far outstrips supply.

Researchers hope to one day grow replacement organs in the laboratory, ideally from a patient’s own cells. This research is another step in this direction, but there is still a long way to go. The liver tissue grown in the current study was very small, and much more research is needed before it could be tested in humans.

Where did the story come from?

The study was carried out by researchers from Yokohama City University Graduate School of Medicine and other research centres in Japan. It was funded by the Japan Science and Technology Agency, the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Takeda Science Foundation, the Japan IDDM network, and the Yokohama Foundation for Advanced Medical Science.

The study was published in the peer-reviewed scientific journal Nature, and was generally well reported in the media, with just a few issues of note.

The Daily Telegraph story suggests that: “Patients suffering from liver failure could be injected with tiny replacement organs grown from their own stem cells within the next 10 years following new research.” Although promising, the research is still only at an early stage. So, it is difficult to know whether this “10-year” predication is realistic.

Also, the Daily Mail suggests that using this tissue to test new medicines will be able to prevent “disasters such as the ‘Elephant Man’ drug trial, in which six men were left fighting for their lives”. But this type of liver tissue has not yet been used in drugs trials, so whether it could potentially be used in this way is not yet clear.

Even if it is does eventually become used for this purpose, it could not predict all drug side effects. For example, the “Elephant Man” trial mentioned by the Mail was thought to be related to an effect on the human immune system, not an effect on the liver.

What kind of research was this?

This was an animal study in which researchers attempted to grow a functional piece of human liver tissue in mice.

There is a significant shortage of organ donors, so researchers would like to be able to grow whole functioning human organs from stem cells. Stem cells are cells that have the potential to divide and develop into any type of cell in the body.

Although there has been a lot of progress in stem cell research, it has not yet been possible to grow a three-dimensional organ with its blood vessels. The researchers wanted to try to achieve this with human liver tissue.

For more information on recent advances in stem cell science, read our special report, Hope and hype.

What did the research involve?

In this study, researchers used human-induced pluripotent stem cells (iPSCs) to develop and divide, forming small clumps of liver cells. These cells were then transplanted into mice. The researchers wanted to see if the cells would grow into functional liver tissue with its own blood supply.

The researchers grew the human-induced stem cells in the laboratory in conditions that would prompt the cells to start developing into liver cells. They grew them along with the sorts of supporting cells that would be present in normal liver development, as this would promote their development into liver cells. The researchers wanted to see if these cells would form small clumps called “liver buds”, similar to what happens in human embryo development when the liver is forming.

The researchers then intended to test these buds to see if the cells had the characteristics of normal human liver buds. These characteristics included the genes that became “active” and the proteins the cells produced.

They also wanted to see if the liver buds would develop their own blood vessels, again similar to what would happen in human embryo development when the liver is forming.

If the liver buds did develop blood vessels, the researchers planned to transplant them into mice to see if their blood vessels would join up with the mouse’s own blood supply. They proposed to then test whether these liver buds could perform some of the functions that a normal liver performs.

What were the basic results?

The researchers found they could successfully grow three-dimensional liver buds that resembled the liver buds seen in normal human liver development.

The cells in these buds had a pattern of gene activity similar to what would be expected in a developing liver, and contained the different types of cells they would expect to see. The buds also developed their own blood vessels.

When the researchers transplanted the liver buds into the mice, their blood vessels joined onto the mice’s blood supply within two days of being transplanted.

This prompted the immature liver buds to develop into tissue resembling a mature adult liver. This liver tissue was able to do some of the things that the normal human liver does, such as breaking down drugs given to the mice.

How did the researchers interpret the results?

The researchers concluded that – to their knowledge – this was the first study to generate a functional human organ from pluripotent stem cells.

They say that further efforts are needed to be able to translate their techniques into a procedure that can be used for human patients.

Conclusion

This study has developed a technique that allows scientists to generate an immature liver bud with its own blood vessels in the laboratory using human-induced stem cells. The scientists were then able to successfully transplant the liver buds into mice and join it up to the mice’s blood system. When tested, these transplanted liver buds performed some of the functions of normal liver tissue. This is reportedly the first time that this has been achieved.

Because of the shortage of organ donors, researchers would like to be able to grow replacement organs in the laboratory. The difficulties posed by matching a donor’s tissue with the recipient’s means that laboratory-grown organs would ideally be made from a patient’s own cells.

This current research is another step in this direction, but there is still a long way to go. The human liver is a large organ with many essential functions. The liver tissue grown in the current study was small, and much more research will need to go into developing the technique to the stage where it could be used in humans. This will include more research to make sure that lab-grown livers can do all the things our bodies need to survive. 

 

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