title: High Temporal Resolution Detection of Patient-Specific Glucose Uptake from Human ex Vivo Adipose Tissue On-Chip.
abstract: Human tissue in vitro models on-chip are highly desirable to dissect the complexity of a physio-pathological in vivo response because of their advantages compared to traditional static culture systems in terms of high control of microenvironmental conditions, including accurate perturbations and high temporal resolution analyses of medium outflow. Human adipose tissue (hAT) is a key player in metabolic disorders, such as Type 2 Diabetes Mellitus (T2DM). It is involved in the overall energy homeostasis not only as passive energy storage but also as an important metabolic regulator. Here, we aim at developing a large scale microfluidic platform for generating high temporal resolution of glucose uptake profiles, and consequently insulin sensitivity, under physio-pathological stimulations in ex vivo adipose tissues from nondiabetic and T2DM individuals. A multiscale mathematical model that integrates fluid dynamics and an intracellular insulin signaling pathway description was used for assisting microfluidic design in order to maximize measurement accuracy of tissue metabolic activity in response to perturbations. An automated microfluidic injection system was included on-chip for performing precise dynamic biochemical stimulations. The temporal evolution of culture conditions could be monitored for days, before and after perturbation, measuring glucose concentration in the outflow with high temporal resolution. As a proof of concept for detection of insulin resistance, we measured insulin-dependent glucose uptake by hAT from nondiabetic and T2DM subjects, mimicking the postprandial response. The system presented thus represents an important tool in dissecting the role of single tissues, such as hAT, in the complex interwoven picture of metabolic diseases.
authors.affiliation: †Department of Industrial Engineering, University of Padova, Padova 35131, Italy.|‡Venetian Institute of Molecular Medicine, Padova, 35129 Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zambon
authors.affiliation: †Department of Industrial Engineering, University of Padova, Padova 35131, Italy.|‡Venetian Institute of Molecular Medicine, Padova, 35129 Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Zoso
authors.affiliation: †Department of Industrial Engineering, University of Padova, Padova 35131, Italy.|‡Venetian Institute of Molecular Medicine, Padova, 35129 Italy.
authors.forename: Onelia
authors.initials: O
authors.lastname: Gagliano
authors.affiliation: †Department of Industrial Engineering, University of Padova, Padova 35131, Italy.|‡Venetian Institute of Molecular Medicine, Padova, 35129 Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Magrofuoco
authors.affiliation: §Department of Medicine, University of Padova, Padova 35128, Italy.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.affiliation: §Department of Medicine, University of Padova, Padova 35128, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.affiliation: ∥Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova 35124, Italy.
authors.forename: Mirto
authors.initials: M
authors.lastname: Foletto
authors.affiliation: ⊥Bioengineering and Applied Physics, Stanford University, Stanford, California 94305, United States.|#Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Quake
authors.affiliation: †Department of Industrial Engineering, University of Padova, Padova 35131, Italy.|‡Venetian Institute of Molecular Medicine, Padova, 35129 Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Elvassore
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D056656:Lab-On-A-Chip Devices
chemical_list: D005947:Glucose