February 23, 1989 - February 23, 2022

  • Date:14WednesdayFebruary 2018

    G-INCPM Special Seminar - Prof. Yaakov Nahmias, Director, Grass Center for Bioengineering, Hebrew Univ., Jerusalem - "Beyond the Chip: Development of a Micro-Physiological Multi-Organ Flux Analyzer

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    11:00 - 12:15
    Nancy and Stephen Grand Israel National Center for Personalized Medicine
    Prof. Yaakov Nahmias
    Director, Grass Center for Bioengineering, Hebrew Univ., Jerusalem
    Department of Biomolecular Sciences
    AbstractShow full text abstract about Organ-on-chip technology aims to replace animal toxicity tes...»
    Organ-on-chip technology aims to replace animal toxicity testing, but thus far demonstrated few advantages over traditional methods. Current methods to evaluate toxicity rely on end-point assays measuring tissue damage and cell death, resulting in limited kinetic and mechanistic information. We present the Tissue Dynamics platform capable of maintaining vascularized 3D liver, cardiac, and neural tissues for over a month in vitro. Tissues acquire physiological structure, physiological activity and show complex metabolic zonation. Tissue-embedded metabolic sensors for oxygen, glucose, lactate and glutamine permit the real-time quantification of intracellular fluxes and tissue level function. Change in metabolic function is the first indication of physiological stress, preceding any detectable damage. Using the Tissue Dynamics platform, we show a new CYP450-idependent mechanism of acetaminophen toxicity that may be responsible for clinically observed nephrotoxicity. We also show that troglitazone, a drug withdrawn from the market due to idiosyncratic toxicity, induces harmful metabolic changes at below the observed threshold for toxic damage. These metabolic changes may underlie troglitazone’s observed idiosyncratic toxicity. Our work marks the importance of tracing function in real-time, demonstrating specific advantages in predicative toxicology.