Researchers at the Fraunhofer Institute for Interfacial Engineering and Biotechnology in Stuttgart, Germany have developed a three-dimensional liver model with a functional blood circulation system that could replace animal tests in a range of early drug development applications.
The 3-D vascularised liver model was created by taking a section of a pig’s small intestine that includes an artery and a vein, removing the animal cells so that only connective tissue proteins and the tubes of the vascular system remain, then lining this network internally with human endothelial cells.
Once artificial blood begins to circulate in the vascular system, cells of all kinds of organs can be grown on the matrix, the researchers explain. Moreover, since the tissue has its own circulatory system, it can be kept alive in a bioreactor for weeks at a time. A computer controls the arterial pressure, temperature and blood flow speed.
According to the Fraunhofer Institute scientists, the new 3-D model opens the door to meaningful results from tests of new drug ingredients on human liver tissue. The system functions in a similar way to a human liver, they say. Nutrients, oxygen and the drug ingredient being tested are transported through the artery into the artificial liver, where liver cells break down the various compounds. The ensuing metabolic waste products are then carried away by the built-in vein.
“The model enables us for the first time to bring drugs into physiological contact with cells, just as in the human body, and to analyse the resultant breakdown products after they have been transformed by the cells,” commented Professor Heike Mertsching of the Fraunhofer Institute. The system will also allow researchers to investigate long-term drug effects and the impact of administering repeatedly a biologically active agent, the scientists added. Moreover, the close approximation of a real liver means the findings can be more readily extrapolated to humans.
