Takanori Takebe Grows Functioning Livers in Stem-Cell Breakthrough

A Yokohama City University stem-cell biologist has created functioning liver tissue by combining iPS cells derived from mature skin cells with cells taken from an umbilical cord.

Takanori Takebe has succeeded in growing three-dimensional structures called “liver buds” that spontaneously form connections with the natural blood vessels of mice and perform the liver function of breaking down drugs in the bloodstream. The development is hailed as the first time that a rudimentary human organ has been produced using induced pluripotent stem (iPS) cells, said Takebe. His work was published Wednesday in the journal Nature.

Takebe’s success is significant because it opens up the possibility of using the technique to create organs difficult to obtain for transplant, including kidneys, lungs and the pancreas as well as livers.

Takebe cultivated liver cell precursors using human iPS cells derived from mature skin cells, then combined them with two types of cells harvested from umbilical cords — blood vessel precursors called endothelial cells, and connective tissue precursor cells called mesenchymal stem cells.

The approach builds on earlier work done by other stem cells researchers showing that co-culturing multiple cell types can help researchers develop physiological three-dimensional tissues in the lab, according to Yoon-Young Jang, director of the Stem Cell Biology Laboratory at Johns Hopkins University School of Medicine. Other Japanese researchers had recently used the technique to cultivate retinal tissue.

Takebe’s team demonstrated the efficacy of the liver buds by transplanting a dozen into the abdomen of mice. They kept the mice alive for a month though their natural liver function had been shut down. The buds didn’t perform all the functions of a mature liver but results suggest that transplanting them into an existing liver allows their function to become integrated into the functioning of the other parts of the organ, like the bile duct system.

Initially the technique may be used to keep liver-failure patients alive by delivering microscopic liver buds through a large vein to the liver to restore as much as 30% of liver function, said Takebe. He estimated that even that type of treatment is at least a decade away due to the need to develop ways to produce enough liver buds efficiently.

In the short term Takebe’s team is collaborating with researchers at a Tokyo biotechnology firm to use liver buds for toxicity testing in drug screening for which bile ducts are not needed. The buds could also be used to screen candidate drugs by modeling patient-specific models of diseases like liver cirrhosis and cancer, suggested Jang of Johns Hopkins.