by Kate Kelland
July 03, 2013
from Reuters Website

Spanish version
 

 

 

 

 

 

Scientists have for the first time created a functional human liver from stem cells derived from skin and blood and say their success points to a future where much-needed livers and other transplant organs could be made in a laboratory.

While it may take another 10 years before lab-grown livers could be used to treat patients, the Japanese scientists say they now have important proof of concept that paves the way for more ambitious organ-growing experiments.

"The promise of an off-the-shelf liver seems much closer than one could hope even a year ago," said Dusko Illic, a stem cell expert at King's College London who was not directly involved in the research but praised its success.

He said however that while the technique looks "very promising" and represents a huge step forward,

"there is much unknown and it will take years before it could be applied in regenerative medicine."

Researchers around the world have been studying stem cells from various sources for more than a decade, hoping to capitalize on their ability to transform into a wide variety of other kinds of cell to treat a range of health conditions.

There are two main forms of stem cells:

  • embryonic stem cells, which are harvested from embryos

  • reprogrammed "induced pluripotent stem cells" (iPS cells), often taken from skin or blood

Countries across the world have a critical shortage of donor organs for treating patients with liver, kidney, heart and other organ failure.

 

Scientists are keenly aware of the need to find other ways of obtaining organs for transplant.

The Japanese team, based at the Okohama City University Graduate School of Medicine in Japan, used iPS cells to make three different cell types that would normally combine in the natural formation of a human liver in a developing embryo - hepatic endoderm cells, mesenchymal stem cells and endothelial cells - and mixed them together to see if they would grow.

They found the cells did grow and began to form three-dimensional structures called "liver buds" - a collection of liver cells with the potential to develop into a full organ.

When they transplanted them into mice, the researchers found the human liver buds matured, the human blood vessels connected to the mouse host's blood vessels and they began to perform many of the functions of mature human liver cells.

"To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells," the researchers wrote in the journal Nature.

Malcolm Allison, a stem cell expert at Queen Mary University of London, who was not involved in the research, said the study's results offered,

"the distinct possibility of being able to create mini livers from the skin cells of a patient dying of liver failure" and transplant them to boost the failing organ.

Takanori Takebe, who led the study, told a teleconference he was so encouraged by the success of this work that he plans similar research on other organs such as the pancreas and lungs.

A team of American researchers said in April they had created a rat kidney in a lab that was able to function like a natural one, but their method used a "scaffold" structure from a kidney to build a new organ.

And in May last year, British researchers said they had turned skin cells into beating heart tissue that might one day be able to be used to treat heart failure.

That livers and other organs may one day be made from iPS cells is an "exciting" prospect, said Matthew Smalley of Cardiff University's European Cancer Stem Cell Research Institute.

"(This) study holds out real promise for a viable alternative approach to human organ transplants," he said.

Chris Mason, a regenerative medicine expert at University College London said the greatest impact of iPS cell-liver buds might be in their use in improving drug development.

"Presently to study the metabolism and toxicology of potential new drugs, human cadaveric liver cells are used, " he said. "Unfortunately these are only available in very limited quantities".

The suggestion from this new study is that mice transplanted with human iPS cell-liver buds might be used to test new drugs to see how the human liver would cope with them and whether they might have side-effects such as liver toxicity.

 

 

 

 

 

 

 

 

 

 

 
 

Scientists Grow a Simple...

Human Liver

...in A Petri Dish
by Michaeleen Doucleff and Bob Stein
July 03, 2013

from NPR Website

Spanish version

 

 

Liver buds" grow in petri dishes.

The rudimentary organs are about 5 mm wide,

or half the height of a classic Lego block.
Courtesy of Takanori Takebe/Yokohama City University Graduate School of Medicine

 

 

Japanese scientists have cracked open a freaky new chapter in the sci-fi-meets-stem-cells era.

 

A group in Yokohama reported it has grown a primitive liver in a petri dish using a person's skin cells. The organ isn't complete. It's missing a few parts. And it will be years - maybe decades - before the technique reaches clinics.

 

Still, this rudimentary liver is the first complex, functioning organ to be grown in the lab from human, skin-derived stem cells.

 

When the scientists transplanted the organ into a mouse, it worked a lot like a regular human liver.

"It's a huge step forward," George Daley, from the Harvard Stem Cell Institute, tells NPR's Rob Stein.

 

 

Not quite yet: A human liver contains bile ducts connecting to the gall bladder.

The proto-livers made in the lab are missing these tubes.

Gray's Anatomy of the Human Body/Wikimedia.org

 

"There have been groups that have attempted to generate liver cells, and that's been promising," says Daley, who wasn't involved in the current study. "This is the first attempt to regenerate the organ by mixing the cells that are critical components of that organ."

Several labs around the world have been trying to grow organs on plastic scaffolds, which offer a three-dimensional surface on which cells can stick.

 

This approach has been used to make tracheas from a person's own cells. And doctors have even transplanted these synthetic organs into a handful of patients.

 

But more complex organs - kidneys, pancreases and livers - have been elusive. So Takanori Takebe and a team at the Yokohama City University tried a more laid-back strategy: They let the cells build their own scaffold.

 

The team took some liver cells (made from a person's induced pluripotent stem cells) and then mixed them with two other cell types - one that makes blood vessels and one that builds connective tissue to hold an organ together.

 

Five days later, Takebe was "completely gobsmacked," by what he saw in the petri dish, he told reporters Tuesday, with the help of a translator. The cell mixtures had assembled into tiny 3-D structures that looked and acted like miniature livers, or "liver buds," as Takebe calls them.

The proto-organs were only about 5 millimeters tall, or half the height of a Lego brick. But the liverettes built their own blood vessels, which allowed Takebe and his team to test-drive them in mice.

 

They plucked the liver buds from the petri dish and then connected them to blood vessels in a mouse. About 10 days later, the buds started working. They broke down human drugs and made blood proteins, as a regular liver would.

 

One proto-organ even saved a mouse from liver failure, Takebe and his colleagues report in the journal Nature.

 

The results are "extremely encouraging," says stem-cell scientist Stuart Forbes, from the University of Edinburgh.

"But there's a significant amount of further research [required] before we could translate this to a clinical therapy for patient," he tells Stein.

First off, the organs are too small to be useful.

 

Doctors would need thousands of them to help a person with liver damage. And the little buds don't form a full liver. They're missing bile ducts, or the tubes that drain away toxins. Plus, Forbes says, there's still a big question about safety. Stem cells tend to form tumors.

 

And the current study doesn't look at the long-term effect of the transplanted liver.

"To perform this in humans, we'd like to see a lot of safety testing," Forbes says.