The application of engineered liver tissues for novel drug discovery

Abstract

Engineered liver models with varying levels of in vivo-like complexities provide investigators with the opportunity to develop assays with sufficient complexity and required throughput. Control over cell-cell interactions and co-culture with stromal cells in both two dimension and three dimension are critical for enabling stable liver models. The validation of liver models with diverse sets of compounds for different applications, coupled with an analysis of cost:benefit ratio, is important for model adoption for routine screening. Ultimately, engineered liver models could significantly reduce drug development costs and enable the development of more efficacious and safer therapeutics for liver diseases.

Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease

“…The utilisation of advanced or organ-on-a-chip type in vitro culture systems that more closely mimic the microenvironment of the liver are now established as a method for maintaining the functions of primary human hepatocytes in vitro and preventing rapid dedifferentiation[20,21]. We have utilised a 3D perfused platform to develop an all human in vitro model of NAFLD.…”

“…Using organ-on-a-chip and microfluidic approaches, cell culture micro-environments can be created that recapitulate the mechanical forces, tissue-tissue interfaces, and spatiotemporal chemical gradients of living organs[21,22]. Numerous advanced liver models have been described, which improve the long-term functionality of hepatocytes compared with 2D monocultures or simple 3D spheroid cultures[20,21]. …”

Fabrication and Characterization of Heparin/Collagen Sponge for in Vitro Differentiation of Wharton’s Jelly-Derived Mesenchymal Stem Cells into Hepatocytes

“…Many in vitro models have been introduced to improve the hepatocyte activities and morphology (43). Such a model tries to imitate the in vivo niche complexities (44). The collagen/heparin scaffold can be introduced to be used in drug discovery and toxicological assessments as the data 8 Hepat Mon.…”

Engineered Liver Platforms for Different Phases of Drug Development

“…Such models can also aid in phenotypic drug discovery against liver diseases (i.e. hepatitis B/C viral infections, fatty liver disease, fibrosis, carcinoma) [7]. Primary human hepatocytes (PHHs) are ideal for creating human liver models; however, their liver-specific functions (see Box 1) rapidly decline in conventional culture formats, which leads to a low (<50%) sensitivity for DILI prediction [6,8].…”