Adipose-on-a-chip: a dynamic microphysiological <i>in vitro</i> model of the human adipose for immune-metabolic analysis in type II diabetes

Liu, Yunxiao; Kongsuphol, Patthara; Chiam, Su Yin; Zhang, Qing Xin; Gourikutty, Sajay Bhuvanendran Nair; Saha, Sujoy; Biswas, Subhra K.; Ramadan, Qasem

doi:10.1039/c8lc00481a

Cited by 52 publications

(47 citation statements)

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“…However, although organ-on-a-chip research has burgeoned in recent years, and numerous platforms have been developed for many organs and tissues, WAT appears to have been largely overlooked, and only a few relevant efforts have been undertaken 25 . Several research groups injected pre-adipocytes from murine 35,36 or human [37][38][39] sources into microfluidic chambers, and were able to subsequently induce adipogenesis. Others directly introduced primary adipocytes from mice into mesoscopic, perfused reservoirs 40 .…”

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confidence: 99%

WAT-on-a-chip integrating human mature white adipocytes for mechanistic research and pharmaceutical applications

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Kromidas

et al. 2020

Sci Rep

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Obesity and its numerous adverse health consequences have taken on global, pandemic proportions. White adipose tissue (WAt)-a key contributor in many metabolic diseases-contributes about one fourth of a healthy human's body mass. Despite its significance, many WAT-related pathophysiogical mechanisms in humans are still not understood, largely due to the reliance on non-human animal models. In recent years, Organ-on-a-chip (OoC) platforms have developed into promising alternatives for animal models; these systems integrate engineered human tissues into physiological microenvironment supplied by a vasculature-like microfluidic perfusion. Here, we report the development of a novel OoC that integrates functional mature human white adipocytes. The WAT-on-achip is a multilayer device that features tissue chambers tailored specifically for the maintenance of 3D tissues based on human primary adipocytes, with supporting nourishment provided through perfused media channels. The platform's capability to maintain long-term viability and functionality of white adipocytes was confirmed by real-time monitoring of fatty acid uptake, by quantification of metabolite release into the effluent media as well as by an intact responsiveness to a therapeutic compound. The novel system provides a promising tool for wide-ranging applications in mechanistic research of WAtrelated biology, in studying of pathophysiological mechanisms in obesity and diabetes, and in R&D of pharmaceutical industry. The global obesity pandemic poses one of today's biggest challenges to public health. Each year, 2.8 million people die from causes related to overweight or obesity 1. Since the 1970s, the worldwide prevalence of obesity has nearly tripled, also leading to an upsurge in associated comorbidities such as type 2 diabetes (Fig. 1a) 2. Future projections reveal the gravity of this public health crisis: the prevalence rates of childhood obesity are increasing at an alarming pace 3 , and by 2030, more than 50% of U.S. adults are predicted to be obese 4. White adipose tissue (WAT) is the principal organ in obesity. In healthy human adults, WAT comprises approximately 20-25% of the total body mass, thus constituting the second largest organ, after the skin. In obese individuals, WAT's contribution to the total body mass may become as high as 50% (Fig. 1b) 5. WAT is tightly involved in the two most important functions of an organism-energy homeostasis and reproduction 6. In energy homeostasis, not only does WAT act as the main storage site of excess dietary energy (Fig. 1c), it also performs crucial endocrine and metabolic functions (Fig. 1d) 7,8. WAT can sense the body's energy status, and respond appropriately, either by storing fuel, in the form of triacylglycerides, or by releasing it as glycerol and fatty acids, for ultimate delivery to organs in need. While this classically described role of WAT already entailed extensive crosstalk between WAT and other organs, its inter-organ communications extend beyond simple feedback loops activated by fed-or fast...

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confidence: 99%

WAT-on-a-chip integrating human mature white adipocytes for mechanistic research and pharmaceutical applications

Rogal

Binder

Kromidas

et al. 2020

Sci Rep

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“…To date, several types of cells, such as induced pluripotent stem (iPS) cells, neural cells, cardiac cells, liver cells, cancer cells, have been employed for microfluidic 3D cell culture. Accordingly, a number of organ‐on‐a‐chip systems have been successfully built to mimic in vivo organs of blood vessel, muscle, bone, lungs, skin, liver, brain, gut, kidney, placenta, islet, endocrine tissue, and adipose tissue . These systems can also be used to recapitulate diverse physiological (e.g., blood–brain barrier (BBB), bone–cartilage interface regeneration) and disease processes (e.g., cancer, dermal wound, inflammation).…”

Section: Microfluidics‐based Bioanalysismentioning

confidence: 99%

Microfluidics for Biomedical Analysis

et al. 2019

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Many new techniques and materials have been applied to microfluidic systems in the past decade, and integrated microfluidic chips have become powerful platforms for realizing highly sensitive, high throughput, and low‐cost analysis. This article reviews the latest advancements of microfluidic platforms for biological and biomedical analysis in the fields of fundamental biology research, clinical application, food safety, and environmental monitoring, with a focus on nucleic acid‐based molecular diagnosis and protein‐based immunodiagnosis. The combination of microfluidics with advanced techniques (e.g., nanotechnology, 3D printing, deep learning) would offer innovative new tools for bioanalyses. The current challenges and the future developments of microfluidic technologies for clinical applications are also discussed. It is anticipated that this review will be beneficial to promoting microfluidics toward a broad range of applications in the future.

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“…During the last decade, these findings have led to the massive efforts regarding the development of microfluidic organs-on-a-chip mimicking the entire human body [148,149]; in fact, at least one microfluidic-based model has been made to reproduce lung [147,[150][151][152], gut [153][154][155][156][157], brain [158][159][160], eye [161,162], skin [163,164], liver [165][166][167][168], kidney [169,170], pancreas [171,172], adipose tissue [173,174], and heart [175][176][177] (Figure 5). An overview of all these organs-on-a-chip is beyond the scope of the present review, but we want to focus on some examples related to their application to toxicology.…”

Section: Organs- Organoids-on-a-chip and 3d Printingmentioning

confidence: 99%

Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis

et al. 2020

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The last decades of biological, toxicological, and pharmacological research have deeply changed the way researchers select the most appropriate ‘pre-clinical model’. The absence of relevant animal models for many human diseases, as well as the inaccurate prognosis coming from ‘conventional’ pre-clinical models, are among the major reasons of the failures observed in clinical trials. This evidence has pushed several research groups to move more often from a classic cellular or animal modeling approach to an alternative and broader vision that includes the involvement of microfluidic-based technologies. The use of microfluidic devices offers several benefits including fast analysis times, high sensitivity and reproducibility, the ability to quantitate multiple chemical species, and the simulation of cellular response mimicking the closest human in vivo milieu. Therefore, they represent a useful way to study drug–organ interactions and related safety and toxicity, and to model organ development and various pathologies ‘in a dish’. The present review will address the applicability of microfluidic-based technologies in different systems (2D and 3D). We will focus our attention on applications of microchip electrophoresis (ME) to biological and toxicological studies as well as in drug discovery and development processes. These include high-throughput single-cell gene expression profiling, simultaneous determination of antioxidants and reactive oxygen and nitrogen species, DNA analysis, and sensitive determination of neurotransmitters in biological fluids. We will discuss new data obtained by ME coupled to laser-induced fluorescence (ME-LIF) and electrochemical detection (ME-EC) regarding the production and degradation of nitric oxide, a fundamental signaling molecule regulating virtually every critical cellular function. Finally, the integration of microfluidics with recent innovative technologies—such as organoids, organ-on-chip, and 3D printing—for the design of new in vitro experimental devices will be presented with a specific attention to drug development applications. This ‘composite’ review highlights the potential impact of 2D and 3D microfluidic systems as a fast, inexpensive, and highly sensitive tool for high-throughput drug screening and preclinical toxicological studies.

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Adipose-on-a-chip: a dynamic microphysiological in vitro model of the human adipose for immune-metabolic analysis in type II diabetes

Abstract: Infiltration of immune cells into adipose tissue is associated with chronic low-grade inflammation in obese individuals.

Cited by 52 publications

References 51 publications

WAT-on-a-chip integrating human mature white adipocytes for mechanistic research and pharmaceutical applications

WAT-on-a-chip integrating human mature white adipocytes for mechanistic research and pharmaceutical applications

Microfluidics for Biomedical Analysis

Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis

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