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.
Highlights
Individualized genetic factors contribute to disease susceptibility and severity [1,2], drug tolerance [3], and drug-induced liver injury (DILI) [4]
The use of the liver-on-a-chip to model hepatitis virus infection provides a useful platform for individualizing treatments; liver-stage malaria is still under investigation
Integration with biosensors to enhance the utility of the liver-on-a-chip allows real-time or kinetic monitoring of cell functions, leading to novel biological and mechanistic insights that might be a target for new therapeutic approaches
Summary
Individualized genetic factors contribute to disease susceptibility and severity [1,2], drug tolerance [3], and drug-induced liver injury (DILI) [4]. Organoids represent physiologically relevant systems for dissecting tissue development [11,12] and modeling human diseases [13], including infectious diseases [14,15]. Greater physiological relevance to human organs could be obtained, including the liver [17,18], lung [19], kidney [20], heart [21], intestine [22] or multiple organs [23] Both systems are capable of functioning as human tissue In Vivo at efficiencies higher than those of conventional 2D cell culture. We review evidence of individual responses to drugs against hepatotropic infectious diseases and advances in current liver-on-a-chip models of those diseases and drug-induced toxicity. A combination of liver-on-a-chip technology with biosensors is reviewed for the assessment of hepatocyte viability and functions, and some novel biological insights are needed for the development of therapy
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