In vitro micro-physiological model of the inflamed human adipose tissue for immune-metabolic analysis in type II diabetes

Sci Rep. 2019 Mar 20;9(1):4887. doi: 10.1038/s41598-019-41338-3.


Chronic inflammation mediated by the interaction of immune cells and adipocytes is a key underlying factor in obesity-associated type 2 diabetes mellitus (T2DM). Therefore, methods to investigate adipocyte-immune cells interaction and their immuno-metabolic status in obese/T2DM subjects not only serve as an early indicator of disease development but also provide an insight into disease mechanism. A microfluidic-based in vitro model of the human adipose that is interfaced with a co-culture of immune cell has been developed for in vitro immune-metabolic analysis. This miniaturized system integrates a biologically active in vitro cellular system within a perfusion-based microfluidic device for mimicking the major processes that characterize the interaction of adipose tissue with immune cells. A viable immune competent model of the adipocytes/PBMCs co-culture has been demonstrated and characterized. Our testing results showed that the inflammatory cytokine profile obtained from the on-chip culture agrees with those from static transwell based co-culture with more intense responses observed in the chip-based system. The microfluidic chip also allows time-resolved measurement of cytokines that provide reliable data and detailed mechanisms of inflammation. In addition, glucose uptake by the adipocytes from the chip-based cultures showed correlated insulin responsivity/resistivity to the expression of the cytokine profile in different dynamic culture conditions. Testing of the known diabetic drug, metformin, and neutraceutical compound, omega-3, on-chip show agreeable results as compared to the previously reported data. This organotypic culture system offers a physiologically relevant model that exhibits a key characteristic of type 2 diabetic adipose tissues and can be used to study the T2DM mechanisms and diabetic drug screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes* / immunology
  • Adipocytes* / metabolism
  • Adipocytes* / pathology
  • Adipose Tissue / immunology
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Cells, Cultured
  • Coculture Techniques / methods*
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 2* / immunology
  • Diabetes Mellitus, Type 2* / metabolism
  • Humans
  • Inflammation* / immunology
  • Inflammation* / metabolism
  • Insulin / metabolism
  • Lab-On-A-Chip Devices
  • Leukocytes, Mononuclear / cytology
  • Microfluidics / instrumentation
  • Microfluidics / methods*
  • Models, Biological


  • Cytokines
  • Insulin