Scientists produce functional human livers from stem cells

Scott Sutherland

For the very first time, scientists have succeeded in creating a functional, three-dimensional human liver from stem cells, bringing medicine one step closer towards having 'off-the-shelf' transplant organs.

The scientists created tiny liver 'buds', roughly 4 millimetres wide, by bringing together the same types of human cells that combine when the liver starts to grow in the human embryo. Rather than using embryonic stem cells as their 'base', though, the scientists reprogrammed mature human skin cells back into an embryonic state — producing 'induced pluripotent stem cells' or iPSCs. They then added cells taken from umbilical cord blood — called endothelial cells — which create the lining of blood vessels, and another type called mesenchymal stem cells, which go into producing bone, cartilage and fat tissues.

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The buds that grew from this combination of cells not only formed liver tissue, but they also formed a network of blood vessels throughout the tissue. When these buds were transplanted into mice that were suffering from liver failure, they took over various liver functions, keeping the mice alive, and the buds even connected up with the surrounding blood vessels and kept growing.

The most amazing part about this entire discovery is that it essentially happened as an unexpected result. One of the study leaders, Takanori Takebe, from Yokohama City University in Japan, was simply working on a way to create 'vascularized' liver tissue — that is, tissue with blood vessels running through it — which has, so far, been very difficult to do. Some trials have used artificial scaffolding to form the growing cells into the right shape, and others have just grown pure cultures of cells, but Takebe tried combining different types of cells together at the same time. He found that, as they grew, they organized themselves into three-dimensional structures.

"We just simply mixed three cell types and found that they unexpectedly self-organize to form a three-dimensional liver bud — this is a rudimentary liver," Takebe told BBC News. "And finally we proved that liver bud transplantation could offer therapeutic potential against liver failure."

After that discovery, it took hundreds of tries to get up to the stage of making these tiny liver buds.

"The strategy is very promising, and represents a huge step forward," said Dr Dusko Ilic, a stem cell scientist at King's College London, according to BBC News.

"Although the promise of an off-the-shelf-liver seems much closer than one could hope even a year ago, the paper is only a proof of concept. There is much unknown and it will take years before it could be applied in regenerative medicine."

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So, it could be years yet before this type of research actually produces human organs for transplant, but if this self-organization technique can be developed further, it could help address a drastic shortage of human livers for transplant. According to the Canadian Institute for Health Information, between 2002 and 2011, there were a total of 4,419 liver transplants in Canada, but another 5,994 people remained on the donor waiting list and 966 died while waiting.

According to Nature, Takebe hopes that these tiny buds can be made even smaller, so that they can be introduced into a patient's blood stream, and he also thinks that this method could work for other organs, like the lungs, kidneys and pancreas.

(Photo courtesy: Fabrizio Bensch/Reuters)

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