Human ‘mini-livers’ created from stem cells

Human 'mini-livers' have been observed functioning in the bodies of mice similar to this. Picture: AP
Human 'mini-livers' have been observed functioning in the bodies of mice similar to this. Picture: AP
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Human “mini-livers” have been created from stem cells and observed functioning in the bodies of mice.

Scientists say liver failure patients could be given similar implants in another 10 years.

The livers were built by combining together three different cell types, including one derived from artificially made stem cells.

Placed together, they spontaneously organised themselves into five millimetre-wide “liver buds” in laboratory dishes.

The buds were then transplanted into mice with liver failure where they developed a blood supply and grew into mature organs.

Although many hurdles still need to be crossed before building new livers can be considered for humans, the grafts passed critical function tests.

Not only did they generate specific liver proteins, but they were able to break down and detoxify potentially harmful compounds. Survival of the terminally ill mice was also significantly improved.

Writing in the journal Nature, the Japanese scientists said: “To our knowledge this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells.

“Although efforts must ensue to translate these techniques to treatments for patients, this proof-of-concept demonstration of organ-bud transplantation provides a promising new approach to study regenerative medicine.”

Professor Takanori Takebe, from Yokohama City University, who led the team, predicted the first human transplants in 10 years.

“We are now planning to advance the techniques in the patient,” he said.

“The most important step is how to make a huge amount of liver buds for transplant use because the liver is the largest organ in the body.”

Meanwhile the researchers are already investigating whether the “bud” technique can be extended to other organs such as the pancreas and kidney.

The process mimics what happens during embryonic development, when similar organ buds develop in the womb.

It involved the use of partially differentiated pluripotent stem (iPS) cells, created by tweaking the genes of ordinary skin cells to make them revert to an embryonic state.

Being pluripotent means they behave like embryonic stem cells, having the potential ability to develop into any kind of tissue in the body.

The iPS cell-derived “hepatic progenitors” - liver cell precursors - were combined with connective tissue stem cells and endothelial cells that line blood vessel walls.

“We just simply mixed three cell types, including the human iPS-derived hepatic progenitors, and found that they unexpectedly self-organise to form a three dimensional liver bud,” said Prof Takebe. “This is a rudimentary liver.

“After transplantation of the liver buds, their internal vasculature gets functional and matures in to functional liver tissue. Finally, we proved that liver bud transplantation could offer therapeutic potential against liver failure.”

British experts hailed the research as a major step forward while stressing the many challenges that still had to be overcome.

Stem cell biologist Professor Malcolm Alison, from Queen Mary, University of London, said: “This science opens up the distinct possibility of being able to create mini-livers from the skin cells of a patient dying of liver failure, and when transplanted would not be subjected to immune rejection as happens with conventional transplants today.”

Transplant expert Professor Stuart Forbes, from the Medical Research Council Regenerative Medicine, University of Edinburgh, said: “Although exciting, there is still a lot more research needed before this approach could be applied to patients with liver disease.

“The liver buds were small and scaling up to a ‘human relevant size’ may be a challenge, as will creating a true liver structure.

“A further issue is that we are not clear about the long term stability of these stem cell derived cells within a recipient - this would need to be proven before clinical use could be envisaged.”

As well as being developed as replacement organ tissue, the liver buds could also serve as laboratory tools for testing drug toxicity, said the scientists.

The liver is one of the body’s most vital organs and essential to survival. It performs a range of functions including detoxification, protein synthesis and the production of biochemicals necessary for digestion, and plays a major role in metabolism.

Each year more than 16,000 people die from liver disease in the UK, and between 600 and 700 liver transplants are performed.

In the past 20 years, the number of people in the UK who could benefit from a liver transplant is believed to have increased by 90%, but the availability of donor organs has remained unchanged.

Fresh pressure on donor law

THE Scottish Government is facing fresh pressure to follow Wales by backing a controversial “opt-out” system of organ donation when it publishes new plans this month.

The British Medical Association in Scotland yesterday said ministers in Edinburgh should follow the lead of the devolved government in Cardiff which yesterday became the first in the UK to support the plan.

It means instead of “opting-in” to become an organ donor, people will have to specifically ask not to be considered. Backers in Scotland say the move would help slash the waiting list of more than 600 people awaiting a transplant.