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Organovo's 3-D bioprinted liver effectively models drug-induced injury

Organovo researchers developed a 3-D bioprinted liver that effectively modeled drug-induced injury and discerned highly related compounds with different profiles, according to a study published in PLoS One.

“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,” Sharon Presnell, chief scientific officer at Organovo, said in a press release. “Our durable and reproducible model can also be used to measure cell-type specific responses and investigate toxicity mechanisms to develop alternative solutions.”

Drug-induced liver injury is the most common cause of acute liver failure and post-market drug withdrawals, the researchers wrote. Although liver models can provide important insights about the human tissue response in the pre-clinical setting, existing models lack longevity and tissue-level complexity. To create an improved model, Presnell and colleagues developed a 3-D bioprinted liver composed of primary human parenchymal and non-parenchymal cell populations. Their model displays distinct intercellular hepatocyte junctions, CD31+ endothelial networks and desmin positive, smooth muscle actin negative quiescent stellates.

The researchers found the tissues maintained levels of adenosine triphosphate, albumin and drug-induced enzyme activity of cytochrome P450 for over 4 weeks in culture. To assess the model’s ability to mimic tissue-level DILI, the researchers evaluated the dose response of Trovafloxacin — whose toxicity was unable to be monitored in the standard pre-clinical 2-D models — and compared it with Levofloxacin, which is non-toxic. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses no greater than 4 µm and was observed without lipopolysaccharide stimulation in the absence of resident macrophages.

These results show that 3-D bioprinted liver tissues can effectively model DILI and can distinguish between highly related compounds with different profiles, the researchers wrote.

“This publication clearly shows the outstanding performance of Organovo’s 3D bioprinted human liver tissues when compared to traditional preclinical tests in replicating human drug response at the tissue level,” Presnell said in the release. “This data set clearly supports the use of Organovo’s 3D bioprinted human liver tissues in preclinical testing for drug-induced liver toxicity to potentially reduce the risk of toxic drugs reaching patients and avoid costly late-stage clinical failures.” – by Will Offit

Disclosure: Nguyen and Presnell report employment by Organovo Holdings Inc. Please see the full study for all other researchers’ relevant financial disclosures.