Progress and Challenges in the Use of a Liver-on-a-Chip for Hepatotropic Infectious Diseases

Abstract

The liver is a target organ of life-threatening pathogens and prominently contributes to the variation in drug responses and drug-induced liver injury among patients. Currently available drugs significantly decrease the morbidity and mortality of liver-dwelling pathogens worldwide; however, emerging clinical evidence reveals the importance of host factors in the design of safe and effective therapies for individuals, known as personalized medicine. Given the primary adherence of cells in conventional two-dimensional culture, the use of these one-size-fit-to-all models in preclinical drug development can lead to substantial failures in assessing therapeutic safety and efficacy. Advances in stem cell biology, bioengineering and material sciences allow us to develop a more physiologically relevant model that is capable of recapitulating the human liver. This report reviews the current use of liver-on-a-chip models of hepatotropic infectious diseases in the context of precision medicine including hepatitis virus and malaria parasites, assesses patient-specific responses to antiviral drugs, and designs personalized therapeutic treatments to address the need for a personalized liver-like model. Second, most organs-on-chips lack a monitoring system for cell functions in real time; thus, the review discusses recent advances and challenges in combining liver-on-a-chip technology with biosensors for assessing hepatocyte viability and functions. Prospectively, the biosensor-integrated liver-on-a-chip device would provide novel biological insights that could accelerate the development of novel therapeutic compounds.

Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review

“…Additionally, recent advances in the bioscience and stem cell field have developed various in vitro models, such as organoids, organ-on designed for reproducing human tissues and organs, being useful in researching novel treatments (Jin et al, 2021;Kulkeaw et al, 2021;Shinozawa et al, 2021). Therapy based on the mesenchymal stem cells (MSCs), is an innovative current method commonly preferred due to their advantages as broad therapeutic potential and easy accessibility.…”

Sensors-integrated organ-on-a-chip for biomedical applications

“…It is characterized by a hexagonal-shaped microarchitecture filled with distinct hepatocytes, with the central vein located at the center and the portal triads (consisting of the hepatic artery, portal vein, and bile duct) located at each of the six apex sites. To further reveal the relationships between functionality and anatomical structures of liver, OOC technology has been utilized to establish liver-on-achip (liver-OOCs) by culturing diverse hepatocytes within artificial lobule-like microstructures in vitro in numerous manners, including traditional 2D planar culture, 3D spheroid culture, matrix-dependent culture, layer deposition, 3D bioprinting, and so on [122][123][124][125]. These biomimetic microenvironments could replicate the natural liver conditions to maximal extent.…”

iPSC-derived cells for whole liver bioengineering

“…Liver diseases are a global concern, contributing to two million deaths annually ( Ehrlich et al, 2019 ). These conditions encompass, according to the new nomenclature ( Rinella et al, 2023 ): alcohol-associated liver disease (ALD) ( Moradi et al, 2020 ), metabolic dysfunction-associated steatotic liver disease (MASLD), which includes metabolic dysfunction-associated steatohepatitis (MASH) ( Soret et al, 2021 ), as well as Hepatitis B and C ( Kulkeaw and Pengsart, 2021 ), and drug-induced liver injury (DILI) ( Skardal et al, 2020 ). If left untreated, liver diseases progress to severe prognostic conditions, such as cirrhosis and hepatocellular carcinoma (HCC), often culminating in irreversible liver failure ( Younossi et al, 2019 ).…”