Tiny stem-cell livers grown in laboratory
By James GallagherHealth and science reporter, BBC News
Tiny functioning human livers have been grown from stem cells in the laboratory by scientists in Japan.
They said they were “gobsmacked” when liver buds, the earliest stage of the organ’s development, formed spontaneously.
The team, reporting their findings in Nature, hope that transplanting thousands of liver buds could reverse liver failure.
Experts welcomed the findings, describing them as “exciting”.
Scientists around the world are trying to grow organs in the lab to overcome a shortage of organ donors.
Some patients already have bladders made from their own cells, but dense solid organs such as the liver and kidneys are much harder to produce.
Grow your ownThe team at the Yokohama City University were reproducing the earliest stages of liver development – similar to that in an embryo.
They had mixed three types of cells – two types of stem cells and material taken from the umbilical cord.
The promise of an off-the-shelf-liver seems much closer than one could hope even a year ago”
Dr Dusko IlicKing’s College London
Unexpectedly, the cells began to organise themselves and appeared to curl up to form a liver bud.
These buds were transplanted into mice, where they hooked themselves up with the blood supply and began to function as little livers.
The transplants increased the lifespan of mice with liver failure.
Prof Takanori Takebe said: “We just simply mixed three cell types and found that they unexpectedly self-organise to form a three-dimensional liver bud – this is a rudimentary liver.
“And finally we proved that liver bud transplantation could offer therapeutic potential against liver failure.”
He told the BBC that he was “completely gobsmacked” and “absolutely surprised” when he first witnessed the buds forming.
This is a significant advance for the field of regenerative medicine.
It might seem like science fiction but there are already people walking around today with organs made from stem cells.
A major breakthrough came in 2006 when bladders made from patients’ own cells were implanted. Grown windpipes have also been transplanted.
In regenerative medicine there are four levels of complexity: flat structures such as skin; tubessuch as blood vessels; hollow organs such as the bladder; and solid organs such as the kidney, heart and liver.
The last group is the most difficult as they are complex organs containing many types of tissue.
This is a new approach to growing solid organs and is yet another window on what could be the future of organ transplants.
It is thought that other organs such as the pancreas, kidneys and even the lungs could be developed in the same way. However, turning this into a treatment is still a distant prospect.
The buds are 4-5mm in length but the researchers say they would need to develop buds that are much smaller and could be injected into the blood.
The buds would not grow to be a whole new liver, but would embed themselves in the failing one and restore it.
Dr Varuna Aluvihare, a liver transplant physician at King’s College Hospital in London, told BBC News: “This a great piece of work and as a proof of concept, very interesting.
“The real highlight is that such simple mixtures of cells can differentiate and organise themselves into highly complex tissue structures that function well in an animal model.”
He said the liver was very damaged in chronic liver disease so there were still questions about where the buds were transplanted and how they would function.
The risk of a tumour developing after the transplant would also need to be assessed.
Dr Dusko Ilic, a stem cell scientist at King’s College London, said: “The strategy is very promising, and represents a huge step forward.
“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.”
Prof Chris Mason, the chair of regenerative medicine at University College London, said there might be more immediate benefits for drug testing.
New medicines can be toxic to the human liver in a way which does not show up in animal tests. He said using liver buds might be a better way to test for toxicity.