Researchers in Japan have used human stem cells to create tiny human livers like those that arise early in fetal life. When the scientists transplanted the rudimentary livers into mice, the little organs grew, made human liver proteins, and metabolised drugs as human livers do. They and others caution that these are early days and this is still very much basic research. The liver "buds" did not turn into complete livers, and the method would have to be scaled up enormously to treat a patient. Even then, the investigators say, they expect to replace only 30 per cent of a patient's liver. What they are making is more like a patch than a full liver. But the promise is immense, medical experts say. "This is a major breakthrough of monumental significance," said Dr Hillel Tobias, director of transplantation at the New York University School of Medicine. Tobias is chairman of the American Liver Foundation's national medical advisory committee. "Very impressive," said Eric Lagasse of the University of Pittsburgh, who studies cell transplantation and liver disease. "It's novel and very exciting." The study was published in the journal Nature . Dr Leonard Zon, director of the stem cell research programme at Boston Children's Hospital, said he believed that this was the first time anyone had used human stem cells, created from human skin cells, to make a functioning solid organ as opposed to bone marrow. The investigators, led by Dr Takanori Takebe of the Yokohama City University Graduate School of Medicine, began with human skin cells, turning them into stem cells. By adding various stimulators and drivers of cell growth, they then turned the stem cells into human liver cells and began trying to make replacement livers. They say they stumbled upon their solution. When they grew the human liver cells in petri dishes along with blood vessel cells from human umbilical cords and human connective tissue, that mix of cells, to their surprise, spontaneously assembled itself into three-dimensional liver buds. Then the researchers transplanted the liver buds into mice, putting them in two places: on the brain and into the abdomen. The brain site allowed them to watch the buds grow. The investigators covered the hole with transparent plastic, giving them a direct view. The buds grew and developed blood supplies, attaching themselves to the blood vessels of the mice. The abdominal site allowed them to put more buds in to observe whether the buds were functioning like human livers. They were. They made human liver proteins and metabolised drugs that human livers, not mouse livers, metabolise.