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

Sci Rep. 2020 Apr 20;10(1):6666. doi: 10.1038/s41598-020-63710-4.

Abstract

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-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 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 WAT-related biology, in studying of pathophysiological mechanisms in obesity and diabetes, and in R&D of pharmaceutical industry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, White / cytology
  • Adipocytes, White / drug effects*
  • Adipocytes, White / metabolism
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / drug effects*
  • Adipose Tissue, White / metabolism
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Biological Transport / drug effects
  • Culture Media / chemistry
  • Culture Media / pharmacology*
  • Dimethylpolysiloxanes / chemistry
  • Fatty Acids / metabolism*
  • Humans
  • Isoproterenol / pharmacology
  • L-Lactate Dehydrogenase / metabolism
  • Lab-On-A-Chip Devices*
  • Microtechnology / methods
  • Models, Biological
  • Obesity / drug therapy
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / pathology
  • Primary Cell Culture

Substances

  • Adrenergic beta-Agonists
  • Culture Media
  • Dimethylpolysiloxanes
  • Fatty Acids
  • baysilon
  • L-Lactate Dehydrogenase
  • Isoproterenol