Assay Development and Screening

ExVive™ 3D Bioprinted Tissue Modeling of Liver Injury and Disease In Vitro

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  Kelsey Retting, PhD

  Associate Director
  Organovo Inc.

Successful prediction of candidate drugs can be hampered by the lack of in vitro tools to model complexities of human tissue biology. This translational challenge can result in low safety and efficacy predictability and contribute to attrition in drug development. To bridge this gap, the Organovo NovoGen® Bioprinting Platform was utilized to develop ExVive™ 3D Bioprinted Tissues, fully cellular 3D tissue models fabricated by automated spatially controlled cellular deposition. The multicellular architecture of the 3D model can better recapitulate native tissue structure and function compared to standard in vitro models, allowing for complex, tissue-level phenotypes associated with chronic injury and disease. Biochemical and histological characterization demonstrates that ExVive™ Human Liver Tissue enables detection of compound-induced progressive liver fibrogenesis. Here we characterize progression of TGFβ-mediated induction of fibrosis and blockade by Galunisertib as evidenced by key biomarkers, cytokine production, regulation of fibrotic genes, and collagen deposition, collectively demonstrating the utility of the model for the evaluation of interventional strategies and providing evidence of clinically relevant pathway modulation in vitro.