The mini-livers that Organovo made are just half a millimetre deep and 4 millimetres across but can perform most functions of the real thing. To create them, a printer builds up about 20 layers of hepatocytes and stellate cells – two major types of liver cell. Crucially, it also adds cells from the lining of blood vessels. These form a delicate mesh of channels that supply the liver cells with nutrients and oxygen, allowing the tissue to live for five days or longer. The cells come from spare tissue removed in operations and biopsies.
Existing liver assays, based on single or double layers of cells, only last two days and don't have the same range of functions as the micro-discs.
The realistic structure and functioning of the mini-livers make them good predictors of the toxicity of drugs and other substances. They produce albumin, the liver protein that bulks up blood and ferries hormones, salts and drugs throughout the body. They also make cholesterol, which carries fat in the bloodstream, and produce major detoxification enzymes, called cytochrome P450s, that metabolise drugs in the liver.
Organovo's ultimate goal is to create human-sized structures suitable for transplant; the big hurdle is being able to print larger branched networks of blood vessels to nourish such an organ. The company unveiled the mini-livers at the annual Experimental Biology conference this week in Boston.