@article{74fa6991382c43c8966a6b48f50c011b,
title = "How multi-organ microdevices can help foster drug development",
abstract = "Multi-organ microdevices can mimic tissue-tissue interactions that occur as a result of metabolite travel from one tissue to other tissues in vitro. These systems are capable of simulating human metabolism, including the conversion of a pro-drug to its effective metabolite as well as its subsequent therapeutic actions and toxic side effects. Since tissue-tissue interactions in the human body can play a significant role in determining the success of new pharmaceuticals, the development and use of multi-organ microdevices present an opportunity to improve the drug development process. The devices have the potential to predict potential toxic side effects with higher accuracy before a drug enters the expensive phase of clinical trials as well as to estimate efficacy and dose response. Multi-organ microdevices also have the potential to aid in the development of new therapeutic strategies by providing a platform for testing in the context of human metabolism (as opposed to animal models). Further, when operated with human biopsy samples, the devices could be a gateway for the development of individualized medicine. Here we review studies in which multi-organ microdevices have been developed and used in a ways that demonstrate how the devices' capabilities can present unique opportunities for the study of drug action. We will also discuss challenges that are inherent in the development of multi-organ microdevices. Among these are how to design the devices, and how to create devices that mimic the human metabolism with high authenticity. Since single organ devices are testing platforms for tissues that can later be combined with other tissues within multi-organ devices, we will also mention single organ devices where appropriate in the discussion.",
keywords = "Body-on-a-chip, MPS, Micro-cell culture analogs of PBPKs, Microphysiological systems, Multi-organ microdevices, μCCAs",
author = "Esch, {Mandy B.} and Smith, {Alec S.T.} and Prot, {Jean Matthieu} and Carlota Oleaga and Hickman, {James J.} and Shuler, {Michael L.}",
note = "Funding Information: The authors acknowledge support from the National Institute of Health (NIH) through Grant No. UH2TR000516 . MBE and MLS also acknowledge support from the National Science Foundation (NSF) under grant No. CBET-1106153 . MLS and MBE are also supported by the Cornell Center on the Microenvironment & Metastasis through Award Number U54CA143876 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. AS, COS, and JH acknowledge support from the National Institute of Health (NIH) through Grant No. R01NS050452 , Grant No. R01EB009429 , and Grant No. UH2TR000516 . Funding Information: In order to benefit from experiments with multi-organ microdevices, these systems must reliably replicate human metabolism or at least a subset of human metabolism. While several multi-organ microdevices have been developed for the purpose of demonstrating their usefulness in the drug development process, there are practical challenges that must be overcome if the devices are to be used by the pharmaceutical industry. In regard to device development, current efforts to overcome these challenges aim at improving the usability of the devices and the authenticity with which the human metabolism is mimicked. Currently, in the US, the Defense Advanced Research Projects Agency (DARPA) and the National Institute of Health (NIH) are substantially funding research efforts (Microphysiological Systems Program) towards this goal [77] . In particular, the funded research focuses on developing systems that support the culture of primary cells and stem cells for an extended period of time. These efforts also include the development of a common blood surrogate (cell culture medium). Below we discuss these challenges in more detail. ",
year = "2014",
doi = "10.1016/j.addr.2013.12.003",
language = "English (US)",
volume = "69-70",
pages = "158--169",
journal = "Advanced Drug Delivery Reviews",
issn = "0169-409X",
publisher = "Elsevier",
}