ArticleLab on a chip2018
Microphysiological flux balance platform unravels the dynamics of drug induced steatosis.
Article in Lab on a chip, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Trial
- My cells, my model: immune-competent autologous organ-on-chip systems as a new paradigm in precision medicine.Frontiers in immunology · 2025Review
- Evaluating the Effect of Drug Compounds on Cardiac Spheroids Using the Cardiac Cell Outgrowth Assay in a Microphysiological System.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Bridging systems biology and tissue engineering: Unleashing the full potential of complex 3DBiophysics reviews · 2024Review
- Electro-metabolic coupling in multi-chambered vascularized human cardiac organoids.Nature biomedical engineering · 2023Article
- Recent advances in liver-on-chips: Design, fabrication, and applications.Smart medicine · 2023Review
- Microneedle array facilitates hepatic sinusoid construction in a large-scale liver-acinus-chip microsystem.Microsystems & nanoengineering · 2023Article
- State-of-the-art liver disease research using liver-on-a-chip.Inflammation and regeneration · 2022Review
- Human organs-on-chips for disease modelling, drug development and personalized medicine.Nature reviews. Genetics · 2022Review
- Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment.Nanomaterials (Basel, Switzerland) · 2022Review
- Microfluidic systems for modeling human development.Development (Cambridge, England) · 2022Article
- Microfluidic-Based Oxygen (OBiosensors · 2021Review
- Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Liver-Heart on chip models for drug safety.APL bioengineering · 2021Review
- Human biomimetic liver microphysiology systems in drug development and precision medicine.Nature reviews. Gastroenterology & hepatology · 2021Review
- Mechanism and reversal of drug-induced nephrotoxicity on a chip.Science translational medicine · 2021Article
- Liver-on-a-Chip Models of Fatty Liver Disease.Hepatology (Baltimore, Md.) · 2020Review
- A Human Liver-on-a-Chip Platform for Modeling Nonalcoholic Fatty Liver Disease.Advanced biosystems · 2019Article
- Challenges and Opportunities in the Design of Liver-on-Chip Microdevices.Annual review of biomedical engineering · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 7 countries.
Funding
Abstract
Drug development is currently hampered by the inability of animal experiments to accurately predict human response. While emerging organ on chip technology offers to reduce risk using microfluidic models of human tissues, the technology still mostly relies on end-point assays and biomarker measurements to assess tissue damage resulting in limited mechanistic information and difficulties to detect adverse effects occurring below the threshold of cellular damage. Here we present a sensor-integrated liver on chip array in which oxygen is monitored using two-frequency phase modulation of tissue-embedded microprobes, while glucose, lactate and temperature are measured in real time using microfluidic electrochemical sensors. Our microphysiological platform permits the calculation of dynamic changes in metabolic fluxes around central carbon metabolism, producing a unique metabolic fingerprint of the liver's response to stimuli. Using our platform, we studied the dynamics of human liver response to the epilepsy drug Valproate (Depakine™) and the antiretroviral medication Stavudine (Zerit™). Using E6/E7LOW hepatocytes, we show TC50 of 2.5 and 0.8 mM, respectively, coupled with a significant induction of steatosis in 2D and 3D cultures. Time to onset analysis showed slow progressive damage starting only 15-20 hours post-exposure. However, flux analysis showed a rapid disruption of metabolic homeostasis occurring below the threshold of cellular damage. While Valproate exposure led to a sustained 15% increase in lipogenesis followed by mitochondrial stress, Stavudine exposure showed only a transient increase in lipogenesis suggesting disruption of β-oxidation. Our data demonstrates the importance of tracking metabolic stress as a predictor of clinical outcome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.