Organovo Holdings, Inc. (NASDAQ:ONVO) ("Organovo"), a three-dimensional biology company focused on delivering scientific and medical breakthroughs using its 3D bioprinting technology, today announced a publication in the scientific journal, Toxicological Sciences, which demonstrates the power of Organovo's ExVive Human Liver Tissue to effectively model drug-induced liver injury leading to fibrosis.
Using Organovo's 3D bioprinted human liver tissues, researchers from Organovo, The Institute for Drug Safety Sciences and the University of North Carolina at Chapel Hill were able to reconstruct key aspects of methotrexate and thioacetamide-induced progressive human liver injury in a way that other models, including in vitro cellular models and animal models, have not been able to achieve. Repeated, low-concentration exposure to these compounds enabled the detection and differentiation of multiple modes of liver injury, including hepatocellular damage and progressive fibrogenesis. ExVive Human Liver Tissue was used to track the transient and surging production of immunomodulatory and chemotactic cytokines in a concentration and treatment-dependent manner. In addition, the model showed treatment-dependent upregulation of fibrosis-associated genes, ACTA2 and COL1A1, which mimics the hallmark features of a classic wound-healing response. The publication's lead authors were Leah M. Norona, University of North Carolina at Chapel Hill, and Deborah G. Nguyen, Ph.D., Senior Director of Research & Development at Organovo.
"This data set clearly shows that our ExVive Human Liver Tissue can recapitulate key features of drug, chemical and TGF-B1-induced fibrogenesis at the cellular, molecular, and histological levels and can be used to better understand the onset and progression of human liver injury," said Dr. Sharon Presnell, chief scientific officer, Organovo. "The presence of multiple cell types and the tissue-like architecture make the product uniquely capable of modeling complex disease states and providing a comprehensive and cell-type specific view of the mechanism of toxicity to improve risk assessment of drugs and develop alternative solutions."
"This demonstration of methotrexate-induced fibrosis in our liver model has become a strong driver of customer adoption," said Paul Gallant, general manager, Organovo. "Having data that so clearly shows a capability that has been elusive in the past is very compelling, and we're continuing to build a solid base of customers given the growing validation of ExVive Human Liver Tissue's ability to demonstrate correlation with known clinical results."
Modeling drug-induced liver injury has been challenging because existing preclinical animal models may fail to translate results into humans due to species variations in metabolism, injury response, and ability to repair and regenerate tissue. 2D cell culture models are also used to study liver disease states, but they do not reliably mimic liver structure, function and multicellular architecture. The Company's 3D bioprinting technology creates tissues that are spatially patterned, three-dimensional, and multicellular. Organovo's 3D bioprinted human liver tissues are composed of patient-derived parenchymal (hepatocyte) and non-parenchymal (endothelial and hepatic stellate) cell populations and can provide insights into the dynamic and complex intercellular interactions that occur during drug-induced liver injury. Many drugs, such as methotrexate, offer therapeutic benefits that often outweigh toxicity risks. In these cases, the clinical paradigm is focused on measuring and managing toxicity rather than a requirement that the drug be free from any evidence of toxicity. The ExVive platform stands out as an exceptional tool to model and understand tissue-level toxicity, owing to its durable nature and the presence of multiple tissue-specific cell types that are essential in modulating tissue injury, resistance to injury and recovery.
The publication entitled, "Modeling compound-induced fibrogenesis in vitro using three-dimensional bioprinted human liver tissues," was published online on September 8 and can be found here: toxsci.oxfordjournals.org. |
