Replacing a diseased organ with a new one seemed on the brink of reality in 1998, when stem cells were first isolated from human embryos. In the womb, these cells form into every organ of the body. But trying to recreate this performance in a culture dish had defeated researchers.
Until now. In June, Takanori Takebe at Yokohama City University in Japan described the successful choreography of stem cells to produce tiny liver buds. When transplanted into mice, they hooked up to the blood supply and started working as they should, extending the lives of mice with liver failure.
The researchers succeeded by ensuring the stem cells were not dancing alone but with an ensemble. The prima donnas are the stem cells themselves and the researchers used a supporting cast of a variety of cells known as induced pluripotent stem cells (iPS cells), which behave like embryonic stem cells but can be made from a person’s own cells. The team cultivated these to form primitive liver-like hepatic endoderm cells. Then they added the co-stars which dance alongside endoderm cells in the embryo: endothelial cells that form the lining of blood vessels, and mesenchymal cells that form the middle layers of tissues.
With this ensemble, the cells began the dance for which they were programmed. Over 48 hours they arranged themselves into 4mm liver buds, as in an embryo, which the scientists transplanted into the mice.
Although it will be years before human-size livers are ready for transplantation, even rudimentary liver buds might boost an ailing liver. With the global shortage of transplant livers, researchers hope the report heralds a new era. “This technology could be adapted to improve liver function, and hence extend the lives of patients on the transplant list,” says biologist Rebecca Lim at Monash Institute of Medical Research in Melbourne.