title: Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans.
abstract: Although the process of drug development requires efficacy and toxicity testing in animals prior to human testing, animal models have limited ability to accurately predict human responses to xenobiotics and other insults. Societal pressures are also focusing on reduction of and, ultimately, replacement of animal testing. However, a variety of in vitro models, explored over the last decade, have not been powerful enough to replace animal models. New initiatives sponsored by several US federal agencies seek to address this problem by funding the development of physiologically relevant human organ models on microscopic chips. The eventual goal is to simulate a human-on-a-chip, by interconnecting the organ models, thereby replacing animal testing in drug discovery and development. As part of this initiative, we aim to build a three-dimensional human liver chip that mimics the acinus, the smallest functional unit of the liver, including its oxygen gradient. Our liver-on-a-chip platform will deliver a microfluidic three-dimensional co-culture environment with stable synthetic and enzymatic function for at least 4 weeks. Sentinel cells that contain fluorescent biosensors will be integrated into the chip to provide multiplexed, real-time readouts of key liver functions and pathology. We are also developing a database to manage experimental data and harness external information to interpret the multimodal data and create a predictive platform.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Bhushan
authors.forename: Nina
authors.initials: N
authors.lastname: Senutovitch
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Bale
authors.forename: William J
authors.initials: WJ
authors.lastname: McCarty
authors.forename: Manjunath
authors.initials: M
authors.lastname: Hegde
authors.forename: Rohit
authors.initials: R
authors.lastname: Jindal
authors.forename: Inna
authors.initials: I
authors.lastname: Golberg
authors.forename: O
authors.initials: O
authors.lastname: Berk Usta
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
authors.forename: Lawrence
authors.initials: L
authors.lastname: Vernetti
authors.forename: Albert
authors.initials: A
authors.lastname: Gough
authors.forename: Ahmet
authors.initials: A
authors.lastname: Bakan
authors.forename: Tong Ying
authors.initials: TY
authors.lastname: Shun
authors.forename: Richard
authors.initials: R
authors.lastname: DeBiasio
authors.forename: D
authors.initials: D
authors.lastname: Lansing Taylor
mesh_terms: D000818:Animals; D000933:Antifibrinolytic Agents / Q000633:toxicity; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods
chemical_list: D000933:Antifibrinolytic Agents