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Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans

Bhushan, A and Senutovitch, N and Bale, SS and McCarty, WJ and Hegde, M and Jindal, R and Golberg, I and Berk Usta, O and Yarmush, ML and Vernetti, L and Gough, A and Bakan, A and Shun, TY and Biasio, R and Lansing Taylor, D (2013) Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans. Stem Cell Research and Therapy, 4 (SUPPL.).

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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. © 2013 BioMed Central Ltd.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Bhushan, A
Senutovitch, N
Bale, SS
McCarty, WJ
Hegde, M
Jindal, R
Golberg, I
Berk Usta, O
Yarmush, ML
Vernetti, Lvernetti@pitt.eduVERNETTI
Gough, Agough@pitt.eduGOUGH
Bakan, Aahb12@pitt.eduAHB12
Shun, TYtos8@pitt.eduTOS8
Biasio, R
Lansing Taylor, D
Centers: Other Centers, Institutes, Offices, or Units > Drug Discovery Institute
Date: 20 December 2013
Date Type: Publication
Journal or Publication Title: Stem Cell Research and Therapy
Volume: 4
Number: SUPPL.
DOI or Unique Handle: 10.1186/scrt377
Schools and Programs: School of Medicine > Computational and Systems Biology
Refereed: Yes
Article Type: Review
Date Deposited: 26 Sep 2016 16:04
Last Modified: 03 Jan 2024 12:55


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