Abstract

One of the major obstacles in drug discovery is the lack of in vitro three-dimensional (3D) models that can capture more complex features of a disease.Here we established ain vitrophysiologicalmodel of the metabolicsyndrome (MS) using cell-assembly technique (CAT), which can assemble cells into designated places to form complex 3D structures. Adipose-derivedstromal (ADS) cells were assembled with gelatin/alginate/fibrinogen. Fibrin was employed as an effective material to regulate ADS cell differentiation and self-organization along with other methods. ADS cells differentiated into adipocytes and endothelial cells, meanwhile, the cells were induced to self-organize into an analogous tissue structure. Pancreatic islets were then deposited at designated locations and constituted the adipoinsular axis with adipocytes. Analysis of the factors involved in energy metabolism showed that this system could capture more pathological features of MS. Drugs known to have effects on MS showed accordant effects in this system, indicating that the model has potential in MS drug discovery. Overall, this study demonstrated that cell differentiation and self-organization can be regulated by techniques combined with CAT. The model presented could result in a better understanding of the pathogenesis of MS and the development of new technologies for drug discovery.

Keywords:Cell-assembly technique; Stem cell; Biomimetic material; Self-organize; Metabolicsyndrome; Drug discovery