Drug induced liver injury (DILI) is the leading cause of approved drug withdrawal from the market and presents a major health concern as more than 50% of acute liver failures are caused by DILI. Identification of hepatotoxic compounds in the preclinical phase of drug development is key to preventing DILI, however currently employed animal and two-dimensional (2D) in vitro models often fail to predict clinical hepatotoxicity.
Physiologically relevant and efficient in vitro models that mimic the human liver microenvironment and clinical outcome are necessary. Microphysiological system (MPS) models of the liver, or liver-on-a-chip models, incorporate principal characteristics of the in vivo liver such as 3D structure, co-culture, and perfusion. However, many MPS liver models require complex assembly and therefore are low- throughput, limiting their use in a drug screening capacity.
In this application note, we demonstrate the development and assessment of a 3D microfluidic liver-on-a-chip model in the OrganoPlate®, ready to be used for high-throughput hepatotoxicity screening: the OrganoPlate LiverToxTM.
Benefits of the model:
- A robust and validated liver-on-a-chip model to use for high-throughput hepatotoxicity screening
- Recapitulate the in vivo liver through a 3D three liver-cell type model, without the use of animals
- Perform a compound library screen to assess, rank, and prioritize compounds for follow-up mechanistic studies