Towards an Insulin Resistant Adipose Model on a Chip

Tanataweethum, Nida; Zhong, Franklin L.; Trang, Allyson; Lee, Chaeeun; Cohen, Ronald N.; Bhushan, Abhinav

doi:10.1007/s12195-020-00636-x

Cited by 10 publications

(18 citation statements)

References 83 publications

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“…It recapitulates almost full tissue heterogeneity by integrating not only mature adipocytes but also organotypic endothelial barriers and stromovascular cells, with optional separation of tissue‐resident innate immune cells, specifically ATMs. Especially through its reliance on mature cell types, the introduced system distinguishes itself from all other adipose tissue‐on‐chip approaches that—to the best of our knowledge—rely on in vitro differentiated, [ 37 , 38 , 39 , 40 ] sometimes even murine, [ 41 , 42 , 43 , 44 ] adipose cells; regarding the adipocytes, this aspect is particularly reflected by unilocularity.…”

Section: Discussionmentioning

confidence: 99%

“…[ 26 , 27 , 36 ] Despite some efforts to reflect insulin resistance or WAT immunoregulatory function, almost all WAT‐on‐chip models turn to differentiating AdMSCs/pre‐adipocytes, [ 37 , 38 , 39 , 40 ] or even murine preadipocytes as fundamental cellular components. [ 41 , 42 , 43 , 44 ] Notably, there is a variety of microanalytical fluidic systems, which aim to interrogate adipocyte functionality using microfluidics approaches. [ 45 , 46 , 47 ] While these analytical platforms integrate mature adipocytes and are powerful means to assess highly time‐resolved adipocyte secretions, they are less suited for long‐term culture of adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

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Autologous Human Immunocompetent White Adipose Tissue‐on‐Chip

et al. 2022

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Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In this era of "diabesity", white adipose tissue (WAT) has become a target of high interest for therapeutic strategies. To gain insights into mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models. Leveraging Organ-on-Chip technology, a microphysiological in vitro model of human WAT is introduced: a tailored microfluidic platform featuring vasculature-like perfusion that integrates 3D tissues comprising all major WAT-associated cellular components (mature adipocytes, organotypic endothelial barriers, stromovascular cells including adipose tissue macrophages) in an autologous manner and recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. A precisely controllable bottom-up approach enables the generation of a multitude of replicates per donor circumventing inter-donor variability issues and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity via a flexible mix-and-match approach. This WAT-on-Chip system constitutes the first human-based, autologous, and immunocompetent in vitro adipose tissue model that recapitulates almost full tissue heterogeneity and can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized-and precision medicine applications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autologous Human Immunocompetent White Adipose Tissue‐on‐Chip

et al. 2022

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“…Membranes with pore sizes of 3 and 8 µm are commonly used for Transwell migration assays 55 . The smaller pore-size membrane used in our chips reduced the unwanted spontaneous migration of cells into the other channel, while the delivery of cell culture medium and drugs and waste material disposal were still possible 52 , 56 , 57 . Additionally, Matrigel at a 50% dilution has an average pore size of 2 µm, which is much smaller than the cell dimension, thus allowing the Matrigel to hold cells without hindering molecule transportation 58 .…”

Section: Methodsmentioning

confidence: 99%

Patient-derived pancreatic cancer-on-a-chip recapitulates the tumor microenvironment

et al. 2022

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The patient population suffering from pancreatic ductal adenocarcinoma (PDAC) presents, as a whole, with a high degree of molecular tumor heterogeneity. The heterogeneity of PDAC tumor composition has complicated treatment and stalled success in clinical trials. Current in vitro techniques insufficiently replicate the intricate stromal components of PDAC tumor microenvironments (TMEs) and fail to model a given tumor’s unique genetic phenotype. The development of patient-derived organoids (PDOs) has opened the door for improved personalized medicine since PDOs are derived directly from patient tumors, thus preserving the tumors’ unique behaviors and genetic phenotypes. This study developed a tumor-chip device engineered to mimic the PDAC TME by incorporating PDOs and stromal cells, specifically pancreatic stellate cells and macrophages. Establishing PDOs in a multicellular microfluidic chip device prolongs cellular function and longevity and successfully establishes a complex organotypic tumor environment that incorporates desmoplastic stroma and immune cells. When primary cancer cells in monoculture were subjected to stroma-depleting agents, there was no effect on cancer cell viability. However, targeting stroma in our tumor-chip model resulted in a significant increase in the chemotherapy effect on cancer cells, thus validating the use of this tumor-chip device for drug testing.

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“…Hyperinsulinemia also appears to be involved in SR stress via two mechanisms [ 129 , 130 ]: The IRE1/JNK signaling pathway is activated, contributing to a further reduction in cardiac function [ 131 ]; The onset of an inflammatory state: during diabetic cardiomyopathy, it induces the activation of macrophages, neutrophils, mast cells, platelets, and T lymphocytes, leading to the release of proinflammatory cytokines and other molecules, such as ROS and proteases, which have harmful effects on cardiomyocytes [ 132 ]. The induced inflammatory response contributes to the onset and development of cardiomyopathy and heart failure [ 133 ]. Figure 3 shows the phases that temporally occur during the onset of myocardial damage caused by hyperglycemia in diabetic cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

Effects of Bergamot Polyphenols on Mitochondrial Dysfunction and Sarcoplasmic Reticulum Stress in Diabetic Cardiomyopathy

et al. 2021

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Cardiovascular disease is the leading cause of death and disability in the Western world. In order to safeguard the structure and the functionality of the myocardium, it is extremely important to adequately support the cardiomyocytes. Two cellular organelles of cardiomyocytes are essential for cell survival and to ensure proper functioning of the myocardium: mitochondria and the sarcoplasmic reticulum. Mitochondria are responsible for the energy metabolism of the myocardium, and regulate the processes that can lead to cell death. The sarcoplasmic reticulum preserves the physiological concentration of the calcium ion, and triggers processes to protect the structural and functional integrity of the proteins. The alterations of these organelles can damage myocardial functioning. A proper nutritional balance regarding the intake of macronutrients and micronutrients leads to a significant improvement in the symptoms and consequences of heart disease. In particular, the Mediterranean diet, characterized by a high consumption of plant-based foods, small quantities of red meat, and high quantities of olive oil, reduces and improves the pathological condition of patients with heart failure. In addition, nutritional support and nutraceutical supplementation in patients who develop heart failure can contribute to the protection of the failing myocardium. Since polyphenols have numerous beneficial properties, including anti-inflammatory and antioxidant properties, this review gathers what is known about the beneficial effects of polyphenol-rich bergamot fruit on the cardiovascular system. In particular, the role of bergamot polyphenols in mitochondrial and sarcoplasmic dysfunctions in diabetic cardiomyopathy is reported.

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Towards an Insulin Resistant Adipose Model on a Chip

Cited by 10 publications

References 83 publications

Autologous Human Immunocompetent White Adipose Tissue‐on‐Chip

Autologous Human Immunocompetent White Adipose Tissue‐on‐Chip

Patient-derived pancreatic cancer-on-a-chip recapitulates the tumor microenvironment

Effects of Bergamot Polyphenols on Mitochondrial Dysfunction and Sarcoplasmic Reticulum Stress in Diabetic Cardiomyopathy

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