WAT’s up!? – Organ-on-a-chip integrating human mature white adipose tissues for mechanistic research and pharmaceutical applications

Abstract

Obesity and its numerous adverse health consequences have taken on global, pandemic proportions. White adipose tissue (WAT) -a key contributor in many metabolic diseasescontributes 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 WAT. The WAT-on-a-chip 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 WAT 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 WAT-related biology, in studying of pathophysiological mechanisms in obesity and diabetes, and in R&D of pharmaceutical industry.WAT's up!? -A human WAT-on-a-chip Rogal, Binder, Kromidas, Probst, Schneider, Schenke-Layland, and Loskill

User-Friendly and Parallelized Generation of Human Induced Pluripotent Stem Cell-Derived Microtissues in a Centrifugal Heart-on-a-Chip

“…The centrifugal HoC consists of two microfluidic modules sandwiching a track-etched polyethylene terephthalate (PET) membrane with a pore size of 3 μm (030444 SABEU), which was plasma coated as previously described. 24 Individual modules were fabricated using standard soft lithography and replica molding techniques. 25 Briefly, silicon wafer masters for the two modules, featuring microchannels and chambers with heights of 100 μm, were manufactured by UV lithography, using photoresist (SU-8 50 MicroChem) according to the manufacturer's protocols.…”

Fat-On-A-Chip Models for Research and Discovery in Obesity and Its Metabolic Comorbidities

“…In comparable studies, Rogala et al maintained primary cultures of mature human adipocytes in a microperfusion bioreactor for up to 5 weeks in vitro while maintaining viability and functionality based on fatty acid uptake and lipolytic assays in response to beta-adrenergic agonists. 81 The ability to maintain cultures for such extended periods of time while retaining metabolic functionality and viability are features favorable for drug development screening assays.…”