New liver model for drug tests

In the early stages of drug development, a drug's effect is tested in animal experiments.

For the first time, a 3-D liver model with a working blood circulation system makes it possible to obtain meaningful results from tests of new drug ingredients on human liver tissue.

Pharmaceutical companies invest huge amounts of money in the development of new drugs. To find out how the new substances act, the researchers usually take recourse to animal experiments. But the body of a mouse or a pig reacts differently to the human body. Even the results of tests performed on artificial or immortal cell cultures of human cells are only of limited validity. Scientists at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB have succeeded in producing different types of human tissue such as skin, liver and intestines. The liver model is of particular interest for drug tests. The special feature of the system is that the artificial tissue possesses a functional network of blood vessels. This is known by experts as a 3-D vascularized liver model.

So how do the scientists create three-dimensional tissue models that have their own blood supply? First, they take a piece of a pig’s small intestine, including an artery to supply the blood and a vein to carry it away. Then they remove the animal cells until all that remains besides the proteins of the connective tissue layer are the tubes of the vascular system, which branches out into tiny capillaries like a fan. The scientists line this plexus from the inside with human endothelial cells, as in the real-life archetype. As soon as artificial blood begins to circulate in the vascular system, cells of all kinds of organs can grow on the matrix. Since the tissue has its own blood circulation system, it can be kept alive in a bioreactor for weeks at a time. A computer controls the arterial pressure, the temperature and the flow speed.

The liver model makes it possible to investigate whether any toxins with undesirable side-effects are produced when the new drug ingredients are metabolized. The test system functions in a similar way to the human liver. Nutrients, oxygen and the drug ingredient under test are transported through the artery into the artificial liver. There, liver cells break down the various compounds, and the vein carries away the metabolic waste products. “The model enables us for the first time to bring drugs into physiological contact with cells just as in the human body, and to analyze the resultant breakdown products after they have been transformed by the cells,” explains Professor Heike Mertsching of the IGB. The tissue model even enables the researchers to investigate long-term drug effects and determine the outcome of repeated administration of a biologically active agent. A further benefit is that the findings can more readily be applied to humans.

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