Jul 11, 2016 | By Benedict

Researchers from Organovo and Roche Pharmaceutical Research and Early Development have used Organovo’s 3D printed human liver tissues to model drug-induced liver injury and distinguish between trovafloxacin and levofloxacin, two closely related compounds with different toxicity profiles.

The development of 3D printed human organs is an incredibly important area of medical research. Although the field still in its infancy, many scientists are hopeful that, in the not-too-distant future, patients will be able to obtain artificially fabricated organs to replace defective livers, kidneys, and even hearts. In the meantime, however, 3D printed human tissues are already playing a different yet similarly important role in medicine. Using 3D bioprinted tissue, researchers in the pharmaceutical industry are now able to test the effect of substances upon “human” organs, but without the need for human volunteers. This allows researchers to perform much more radical experiments than would otherwise be possible, since there is no human life at stake.

Organovo, a specialist in 3D bioprinted human tissues, has been providing artificially fabricated tissues for pharmaceutical research for several years now, and a new study conducted by Organovo and Roche, a global healthcare company, has shown that Organovo’s 3D printed human liver tissues can be used to successfully distinguish between the differing toxicity levels of multiple substances. This capability could help pharmaceutical companies identify substances which could potentially produce harmful effects on the human body.

Using Organovo’s 3D bioprinted human liver tissues, the researchers were able to detect the toxicity of trovafloxacin, a third-generation anti-infective drug that was withdrawn from the market one year after being approved after a small proportion of patients died of liver failure. When this substance was initially approved, traditional testing methods were unable to identify its toxicity. The Roche and Organovo researchers, however, were able to distinguish between the toxicity profiles of trovafloxacin and levofloxacin, a structurally related, but non-toxic compound. Organovo will hope that the success of these experiments could pave the way for its 3D printed liver tissues to be used—in conjunction with other methods, such as animal testing and 2D cell culture models—in the testing of future pharmaceutical products.

Histological effects of trovafloxacin on 3D bioprinted liver tissues. Loss of cellular adhesion is indicated by the single arrow; increased hepatocyte necrosis is indicated by the two arrowheads.

The 3D printed human liver tissues produced by Organovo are composed of patient-derived parenchymal (hepatocyte) and non-parenchymal (endothelial and hepatic stellate) cell populations, and are both spatially patterned and three-dimensional. The three-dimensional nature of the tissues enabled the Roche and Organovo researchers to identify distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin-positive, smooth muscle actin-negative quiescent stellates. The 3D printed tissues also maintained metabolically relevant levels of ATP and albumin, as well as drug-induced enzyme activity of cytochrome P450s for more than four weeks in culture—something that 2D cell cultures would be unable to achieve.

“Organovo’s bioprinting technology creates an in vitro system comprising multiple liver cell types in a defined spatial architecture that can be used over time to gather both histopathological and biochemical data for preclinical toxicity testing,” said Dr. Sharon Presnell, chief scientific officer at Organovo. “Our durable and reproducible model can also be used to measure cell-type specific responses and investigate toxicity mechanisms to develop alternative solutions.”

The scientific study, titled “Bioprinted 3D primary liver tissues allow assessment of organ-level response to clinical drug induced toxicity in vitro,” was published on July 7 in the journal PLOS One. Deborah G. Nguyen, Ph.D., Senior Director of Research & Development, was Organovo’s lead author for the paper.



Posted in 3D Printing Application



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