Recent Advances in Body-on-a-Chip Systems

Sung, Jong Hwan; Wang, Ying I.; Sriram, Narasimhan Narasimhan; Jackson, Max; Long, Christopher J.; Hickman, James J.; Shuler, Michael L.

doi:10.1021/acs.analchem.8b05293

Cited by 199 publications

(134 citation statements)

References 166 publications

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“…The lack of multiple cell types and/or organs for testing novel drug candidates as PPAR agonists is a drawback of most in vitro models. Yet, the advancements made to the development of 'human-on-a-chip' models seem promising [89]. Although still much has to be realized [90], the interconnection of in vitro surrogate organs such as liver, pancreas, and adipose tissue, merged with data of humanized animal models, could enable more reliable PPAR-targeted anti-NASH drug testing and thus improve clinical outcomes.…”

Section: Ppar-targeted Preclinical Drug Testingmentioning

confidence: 99%

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Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

Boeckmans

Natale

Rombaut

et al. 2019

Cells

102

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Non-alcoholic fatty liver disease (NAFLD) affects one-third of the population worldwide, of which a substantial number of patients suffer from non-alcoholic steatohepatitis (NASH). NASH is a severe condition characterized by steatosis and concomitant liver inflammation and fibrosis, for which no drug is yet available. NAFLD is also generally conceived as the hepatic manifestation of the metabolic syndrome. Consequently, well-established drugs that are indicated for the treatment of type 2 diabetes and hyperlipidemia are thought to exert effects that alleviate the pathological features of NASH. One class of these drugs targets peroxisome proliferator-activated receptors (PPARs), which are nuclear receptors that play a regulatory role in lipid metabolism and inflammation. Therefore, PPARs are now also being investigated as potential anti-NASH druggable targets. In this paper, we review the mechanisms of action and physiological functions of PPARs and discuss the position of the different PPAR agonists in the therapeutic landscape of NASH. We particularly focus on the PPAR agonists currently under evaluation in clinical phase II and III trials. Preclinical strategies and how refinement and optimization may improve PPAR-targeted anti-NASH drug testing are also discussed. Finally, potential caveats related to PPAR agonism in anti-NASH therapy are stipulated.

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Section: Ppar-targeted Preclinical Drug Testingmentioning

confidence: 99%

“…Yet, mice carrying humanized (hepatic) PPARs could be key for the evaluation of multi-organ targeted anti-NASH therapies [80,81]. In the future, human-based body-on-a chip methodologies might be considered as suitable human-relevant test models [86,89,91].…”

Section: Outlook and Conclusionmentioning

confidence: 99%

Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

Boeckmans

Natale

Rombaut

et al. 2019

Cells

102

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“…Organs‐on‐chips combine tissue engineering principles with microfabrication techniques to assemble addressable tissue units . This paradigm has expanded to many tissues of the human body and integrated systems of multiple disparate tissue units are combined as body‐on‐a‐chip devices . In parallel, induced pluripotent stem (iPS) cell and organoid biology have enabled access to patient‐specific cell populations and improved tissue organization.…”

Section: Applications Of Precision Biomaterialsmentioning

confidence: 99%

Additive Manufacturing of Precision Biomaterials

2019

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Biomaterials play a critical role in modern medicine as surgical guides, implants for tissue repair, and as drug delivery systems. The emerging paradigm of precision medicine exploits individual patient information to tailor clinical therapy. While the main focus of precision medicine to date is the design of improved pharmaceutical treatments based on “‐omics” data, the concept extends to all forms of customized medical care. This includes the design of precision biomaterials that are tailored to meet specific patient needs. Additive manufacturing (AM) enables free‐form manufacturing and mass customization, and is a critical enabling technology for the clinical implementation of precision biomaterials. Materials scientists and engineers can contribute to the realization of precision biomaterials by developing new AM technologies, synthesizing advanced (bio)materials for AM, and improving medical‐image‐based digital design. As the field matures, AM is poised to provide patient‐specific tissue and organ substitutes, reproducible microtissues for drug screening and disease modeling, personalized drug delivery systems, as well as customized medical devices.

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“…In a further innovation, the organ models have been connected in a single system, often called the multiorgan‐on‐a‐chip (MOC), body‐on‐a‐chip, or multiorgan MPS (S. H. Lee & Sung, ; Sung, Wang, Kim, Lee, & Shuler, ). The multiorgan MPS comprises multiple chambers, each of which represents an organ or tissue, and a microfluidic channel that represents blood flow (Sung, Wang, Narasimhan Sriram et al, ). The multiorgan MPS can simulate multiorgan interactions, which makes the system an attractive platform for studying systemic diseases in vitro (Esch et al, ; D. W. Lee, Ha, Choi, & Sung, ; H. Lee et al, ; S. Y. Lee & Sung, ).…”

Section: Introductionmentioning

confidence: 99%

Construction of pancreas–muscle–liver microphysiological system (MPS) for reproducing glucose metabolism

Lee

Choi

et al. 2019

Biotech & Bioengineering

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Although in vitro models are widely accepted experimental platforms, their physiological relevance is often severely limited. The limitation of current in vitro models is strongly manifested in case of diseases where multiple organs are involved, such as diabetes and metabolic syndrome. Microphysiological systems (MPS), also known as organ-on-a-chip technology, enable a closer approximation of the human organs and tissues, by recreating the tissue microenvironment. Multiorgan MPS, also known as multiorgan-on-a-chip or body-on-a-chip, offer the possibility of reproducing interactions between organs by connecting different organ modules. Here, we designed a three-organ MPS consisting of pancreas, muscle, and liver, to recapitulate glucose metabolism and homeostasis by constructing a mathematical model of glucose metabolism, based on experimental measurement of glucose uptake by muscle cells and insulin secretion by pancreas cells. A mathematical model was used to modify the MPS to improve the physiological relevance, and by adding the liver model in the mathematical model, physiological realistic glucose and insulin profiles were obtained. Our study may provide a methodological framework for developing multiorgan MPS for recapitulating the complex interaction between multiple organs. K E Y W O R D Sglucose metabolism, mathematical model, multiorgan MPS, multiorgan-on-a-chip (MOC), pancreas-muscle-liver MPS

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Recent Advances in Body-on-a-Chip Systems

Cited by 199 publications

References 166 publications

Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

Additive Manufacturing of Precision Biomaterials

Construction of pancreas–muscle–liver microphysiological system (MPS) for reproducing glucose metabolism

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