Organovo, a San Diego regenerative medicine company developing bio-printing technology, says it has used its proprietary NovaGen bioprinter to produce 3D samples of human liver cells that show some of the same characteristics as a functional liver in the body.
The results, which Organovo is reporting today at the 2013 Experimental Biology conference in Boston, could have important ramifications for pre-clinical drug discovery. The six-year-old company describes its findings as “highly reproducible,” and says its 3D liver tissue would make it much easier for scientists to test potential drug compounds for liver toxicity.
Organovo says it is the first time scientists have been able to fabricate liver tissue samples on a petri dish that are truly three-dimensional. Organovo says the liver cells, “printed” with droplets of a supportive gel, assembled themselves into a cellular matrix about 20 cell layers thick—roughly two-thirds the thickness of a credit card. More importantly—the fabricated liver tissue produced cholesterol (needed to build and maintain cellular membranes) and expressed enzymes that metabolize drugs and toxins.
Current pre-clinical testing of drug toxicity uses tissue samples that consist of a single layer of liver cells, which flatten out in a petri dish, according to Organovo CEO Keith Murphy. Flattening the shape appears to greatly diminish their cellular function.
Murphy says cultured liver tissue now used to test drug toxicity is supplied by such companies as BD Biosciences and Life Technologies. Organovo is working to begin marketing its 3D liver tissue by next year.
Organovo says its fabricated liver tissue consists of three distinct types of liver cells organized into the kind of cell architecture seen in normal human livers. Organovo says its 3D tissue also showed cellular density and spatial positioning comparable with healthy liver tissue in the body. The company says its fabricated liver tissue even shows the beginnings of microvascular networks—blood vessels.
“We’re showing characteristic liver function that you just don’t see in a 2D liver cell culture,” Murphy says. He acknowledges that the Organovo-produced tissue isn’t completely functional, but it nevertheless represents a significant innovation, “The current model is so inadequate, and just getting halfway to perfection is so useful that we can refine it over time.”
The company says its 3D liver cells also produced such proteins as albumin, fibrinogen, and transferrin—and expressed such key liver enzymes as CYP 1A2 and CYP 3A4.
In addition, Murphy says 2D liver
