Organovo's technique -- first spotted by New Scientist and deemed "highly reproducible" by its creators -- uses its NovaGen bioprinter and a support gel to print 20 layers of liver cells (from donated livers or surgical waste) into a petri dish. It used hepatocytes cells -- which make up about 80 percent of a liver's mass and enable most functions, from protein storage to carbohydrate conversion -- with endothelial and hepatic stellate cells arranged in between. Endothelial cells form the lining of blood vessels, and so the early formation of microvascular networks occurred in the tiny lab liver. This ensured nutrients and oxygen could be delivered throughout the tissue, which is why it is able to survive for five and a half days in the lab outside of the body.
The actual technique is also key -- cells are dropped onto the dish individually to form a honeycomb pattern, which meant the ratio between hepatocyte and the other cells could be managed. It creates a tight mesh-like network of cells that, as it matures, begins to mirror the same formation and cell density of a real liver inside the body.
The liver is incredibly tiny -- just half a millimetre thick and four millimetres wide. Yet this minute organ, with little visual resemblance to the real thing in its petri dish home, manages to replicate key processes done by the real thing. It produced the protein albumin and synthesised plasma glycoproteins fibrinogen and transferrin. These are all vital in getting nutrients, hormones and drugs to the blood and the rest of the body. It also generated fat-carrying cholesterol. For its detoxification functions, the liver also needs to produce certain enzymes including CYP 1A2 and CYP 3A4 -- which this tiny organ precursor also did. Its albumin production was between five and nine times more than in 2D flat cell structures engineered.
