New Scientist – A tiny human liver, just 5 millimetres in size, has been grown inside a mouse. It remains to be seen whether the organ can replicate all liver functions – and if it will be possible to scale up the tiny structure to useable dimensions.
Hideki Taniguchi and Takanori Takebe at Yokohama City University generated induced pluripotent stem cells from human skin cellsMovie Camera, then encouraged them to develop into liver precursor cells. They added two more types of cell – mesenchymal cells, and endothelial cells from umbilical cord blood vessels. Without the aid of any underlying scaffold, the cells “guided themselves” and generated a microstructure almost identical to normal liver tissue, says Takebe.
“We mixed and graded the cells onto the culture dish and they moved to form a cluster,” he says. “It was a surprising outcome from what was, to be honest, an accident.”
NTDTV – The team took stem cells, derived from human skin cells, and placed them in a specially-concocted culture medium. Nine days later, the team detected the same chemicals that hepatocyte, or liver cells, would produce. Endothelial and mesenchymal cells were introduced in the hope of creating a more organ-like environment.
In two days, the tissue had developed into a 5-millimeter long, three-dimensional “liver bud.” The liver-like tissue was implanted into the head of a mouse, where it was able to metabolize some drugs that human livers can handle, but that their murine counterparts cannot. Tests also show much gene expression typical of human livers, the team said.
This marks the first time a functional organ with a vascular network has been grown from stem cells, with enormous potential from the findings.
Transplanting the structure inside the mouse’s skull allowed the researchers to make use of the increased blood flow to the brain to encourage growth of the new tissue.
Within just 48 hours, human blood vessels began to form within the tiny liver, along with human proteins. Levels of glycogen and amino acids in the tissue were also the same as those found in human liver.
“It’s not yet a perfect liver,” says Takebe. “Improvements need to be made, such as the reconstruction of a bile duct.” Other big obstacles yet to be overcome include finding a way to scale up the resulting organ, he adds.
The research team presented their research findings at the International Society for Stem Cell Research annual meeting in Yokohama, Japan, last week, but have yet to publish the work in a peer-reviewed journal.