Real-time monitoring of liver fibrosis through embedded sensors in a microphysiological system

Abstract

Hepatic fibrosis is a foreshadowing of future adverse events like liver cirrhosis, liver failure, and cancer. Hepatic stellate cell activation is the main event of liver fibrosis, which results in excessive extracellular matrix deposition and hepatic parenchyma's disintegration. Several biochemical and molecular assays have been introduced for in vitro study of the hepatic fibrosis progression. However, they do not forecast real-time events happening to the in vitro models. Trans-epithelial electrical resistance (TEER) is used in cell culture science to measure cell monolayer barrier integrity. Herein, we explored TEER measurement's utility for monitoring fibrosis development in a dynamic cell culture microphysiological system. Immortal HepG2 cells and fibroblasts were co-cultured, and transforming growth factor β1 (TGF-β1) was used as a fibrosis stimulus to create a liver fibrosis-on-chip model. A glass chip-based embedded TEER and reactive oxygen species (ROS) sensors were employed to gauge the effect of TGF-β1 within the microphysiological system, which promotes a positive feedback response in fibrosis development. Furthermore, albumin, Urea, CYP450 measurements, and immunofluorescent microscopy were performed to correlate the following data with embedded sensors responses. We found that chip embedded electrochemical sensors could be used as a potential substitute for conventional end-point assays for studying fibrosis in microphysiological systems.

Extracellular Matrix Optimization for Enhanced Physiological Relevance in Hepatic Tissue-Chips

“…It was observed that ECM has a significant impact on the formation of tight junctions. TEER values among different ECMs have a substantial effect on the MPS-based real-time biological assays, as several researchers have employed TEER for estimating cell viability, fibrosis development, and FBS standardization [ 8 , 27 , 28 , 29 ]. It can be concluded that the choice of ECM is vital for developing the most physiologically relevant MPSs.…”

Evaluation of Antimicrobial and Anticancer Activities of Selected Medicinal Plants of Himalayas, Pakistan

“…After 80 to 90% confluency, the cells were expanded up to 3 passages before seeding and washed with Dulbecco’s phosphate buffer saline (DPBS) (Cat# 14190144, ThermoFisher, Waltham, MA, USA) to remove cell debris and metabolites before adding fresh media. Cells at 90% confluency were trypsinized with 0.05% Trypsin-EDTA solution (Cat# 25300054, Thermo Fisher, USA), then suspended in freshly prepared RPMI-1640 media containing a specified concentration of FBS [ 22 , 33 , 34 , 35 ]. Human primary pulmonary alveolar epithelial cells (HPAEpiC) (Science Cell Research laboratories, Carlsbad, CA, USA) were revived according to the manufacturer’s instructions.…”

Microfluidic Organ-on-a-Chip Devices for Liver Disease Modeling In Vitro

“…Next, it implemented the introduction of a range of sensors inside of the chip, comprehending the device overall. For example, Farooqi et al introduced trans-epithelial electrical resistance (TEER) sensors to follow up on the differentiation of cells within microfluidic devices and the integrity of the epithelial layer [ 100 ]. Different types of sensors were effectively introduced by de Hoyos-Vega et al, where enzymatic assays to analyze media from hepatocytes, beads-based immunoassays to evaluate secretion of specific growth factors, and electrochemical biosensor detecting the biomarkers released by hepatocytes were tested in microfluidic liver-on-chip [ 101 ].…”