Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Aleksander Skardal, Sean V. Murphy, Mahesh Devarasetty, Ivy Mead, Hyun-Wook Kang, Young-Joon Seol, Yu Shrike Zhang, Su-Ryon Shin, Liang Zhao, Julio Aleman, Adam R. Hall, Thomas D. Shupe, Andre Kleensang, Mehmet R. Dokmeci, Sang Jin Lee, John D. Jackson, James J. Yoo, Thomas Hartung, Ali Khademhosseini, Shay Soker, Colin E. Bishop, Anthony Atala

ABSTRACT

Many drugs have progressed through preclinical and clinical trials and have been available - for years in some cases - before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues. Few engineered model systems, including the growing variety of organoid and organ-on-a-chip platforms, have so far reflected the interactive nature of the human body. To address this challenge, we have developed an assortment of bioengineered tissue organoids and tissue constructs that are integrated in a closed circulatory perfusion system, facilitating inter-organ responses. We describe a three-tissue organ-on-a-chip system, comprised of liver, heart, and lung, and highlight examples of inter-organ responses to drug administration. We observe drug responses that depend on inter-tissue interaction, illustrating the value of multiple tissue integration for in vitro study of both the efficacy of and side effects associated with candidate drugs. More... »

PAGES

8837

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-08879-x

DOI

http://dx.doi.org/10.1038/s41598-017-08879-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091232024

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28821762


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448 Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, 143-701, Seoul, Republic of Korea
449 Department of Physics, King Abdulaziz University, 21569, Jeddah, Saudi Arabia
450 Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 02139, Cambridge, MA, USA
451 Wyss Institute for Biologically Inspired Engineering, Harvard University, 02139, Cambridge, MA, USA
452 rdf:type schema:Organization
453 https://www.grid.ac/institutes/grid.9811.1 schema:alternateName University of Konstanz
454 schema:name Center for Alternatives to Animal Testing (CAAT), Bloomberg School of Public Health, Johns Hopkins University Baltimore, 615N Wolfe Street, Baltimore, MD, USA
455 Steinbeis CAAT-Europe, University of Konstanz, Universitätstr 10, Konstanz, Baden-Württemberg, Germany
456 rdf:type schema:Organization
 




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