Graduate Student The Chinese University of Hong Kong (CUHK) Hong Kong, Hong Kong
Abstract: Inflammation is a common response observed in liver diseases and if uncontrolled, can lead to irreversible damage and contribute to liver failure. In view of the limitations of current in-vitro models, organ-on-a-chip platforms, which can better mimic human biology, have recently been employed to investigate disease mechanisms and perform high-throughput drug testing. In this project, we aimed to develop a 3D liver-on-a-chip model to investigate liver inflammation. HepG2 cells were cultured alone or together with non-parenchymal liver cells (NPCs), including liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), in 2D and 3D for liver modelling. To simulate inflammation, the different liver cells were exposed to conditioned medium (CM) containing inflammatory cytokines (e.g., IL-6, IL-1β, TNF-α) collected from induced human monocyte cells (ThP-1 cells). After CM treatment, HepG2 cells cultured in both 2D and 3D showed decrease in cell viability and albumin levels. An increase in inflammatory markers such as C-reactive protein and reactive oxygen species levels was observed. For NPCs, LSECs showed a decrease in cell viability and expression of cell specific markers after CM treatment. Meanwhile, increased expression of fibrotic markers was seen in HSCs after CM treatment. When HepG2, LSECs and HSCs were co-cultured in 3D, better cell viability and functionality was observed when compared to 2D co-culture and monoculture. Next, a microfluidic chip was fabricated to perform the co-culture on chip which will be used for testing anti-inflammatory drugs. This liver-on-a-chip platform will serve as a valuable tool for high-throughput screening of potential therapeutics for treating liver inflammatory diseases.
Funding Source: National Key Research and Development Program of China; Research Grants Council of Hong Kong; The Charlie Lee Charitable Foundation – Regenerative Immunology Technologies for the Treatment of COVID-19 and Related Diseases– RMG01
