Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform
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...
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Nature Portfolio
2017
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oai:doaj.org-article:545c3d4e24814f1fb722fae0fa19632f2021-12-02T16:08:23ZMulti-tissue interactions in an integrated three-tissue organ-on-a-chip platform10.1038/s41598-017-08879-x2045-2322https://doaj.org/article/545c3d4e24814f1fb722fae0fa19632f2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08879-xhttps://doaj.org/toc/2045-2322Abstract 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.Aleksander SkardalSean V. MurphyMahesh DevarasettyIvy MeadHyun-Wook KangYoung-Joon SeolYu Shrike ZhangSu-Ryon ShinLiang ZhaoJulio AlemanAdam R. HallThomas D. ShupeAndre KleensangMehmet R. DokmeciSang Jin LeeJohn D. JacksonJames J. YooThomas HartungAli KhademhosseiniShay SokerColin E. BishopAnthony AtalaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
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Medicine R Science Q 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 Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Aleksander Skardal |
| title |
Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform |
| title_short |
Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform |
| title_full |
Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform |
| title_fullStr |
Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform |
| title_full_unstemmed |
Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform |
| title_sort |
multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/545c3d4e24814f1fb722fae0fa19632f |
| work_keys_str_mv |
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