05 Jul 2013, BioSpectrum Bureau , BioSpectrum
Singapore: Japanese scientists have managed to fabricate rudimentary human livers liken those that arise early in fetal life, using human stem cells.
The scientists attained success after the transplantation of these rudimentary livers into mice led to the little organs growing, made human liver proteins and metabolized drugs as human livers do.
The liver buds did not turn into complete livers and researchers said that the method would have to be scaled up largely to make enough replacement liver buds to treat a patient. Even then, they warned that they expect to replace only 30 percent of a patient's liver because what they are making is more like a patch than a full liver.
The study that was first published in the journal Nature was led by Dr Takanori Takebe of the Yokohama City University Graduate School of Medicine. The research 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, resembling the liver at about five or six weeks of gestation in humans.
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 in each animal's skull with transparent plastic, giving them a direct view of the developing liver buds. 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 - 12 buds in each of two places in the abdomen, compared with one bud in the brain - which let the investigators ask if the liver buds were functioning like human livers. They were. They made human liver proteins and also metabolized drugs that human livers - but not mouse livers - metabolize.
Dr Takebe and his colleagues are now focused on scaling up their process so they can try to take it to the clinic, perhaps to treat babies and children whose livers have failed. He estimated they would need hundreds of thousands of liver buds to replace 30 percent of the liver.