Abstract

AbstractOne of the major obstacles in developing multifunctional drugs for the metabolic syndrome (MS) is lack of in vitro models that capture more complex features of the disease. Here we give the first report that establishes an energy metabolic system model using cell-assembly technique which can assemble cells into designated places to form complex three-dimensional structures. Adipose-derived stromal cells were assembled and induced differentiation into adipocytes and endothelial cells; pancreatic islets were then deposited at designated locations and constituted adipoinsular axis with adipocytes. Analysis of the factors involved in energy metabolism showed our system could capture more physiological and pathophysiological features of the in vivo energy metabolism. Drugs known to have effects on MS showed accordant effects in the systems. Construction and study of such multicellular systems could help us better understand pathogenesis of MS, develop new technologies for drug discovery, and foster applications in tissue engineering and metabolomics profiling.

Highlights

  • Tissue engineering endeavored to manufacture tissues and organs, but pay little attention to establish physiological system models[7,8]

  • Metabolic syndrome (MS) is largely presented as energy metabolic turbulence and cardiovascular disease (CVD); adipocytes and β-cells usually constitute adipoinsular axis to regulate energy metabolism[24]; and endothelial cell dysfunction can connect the pathogenesis of energy metabolic turbulence with CVD25

  • Considering the important roles of adipocytes, β-cells and endothelial cells in energy metabolism and MS pathogenesis, we assumed that these types of cell would be required for construction of model for MS

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Summary

Introduction

Tissue engineering endeavored to manufacture tissues and organs, but pay little attention to establish physiological system models[7,8]. In study of complex physiological processes, there is an increasing demand for in vitro 3-D models that can capture more of the relevant complexity than what traditional two-dimensional (2-D) cultures achieve. . Researchers including ourselves have devoted to find out drug targets and establish models for MS20-23. MS is largely presented as energy metabolic turbulence and cardiovascular disease (CVD); adipocytes and β-cells usually constitute adipoinsular axis to regulate energy metabolism[24]; and endothelial cell dysfunction can connect the pathogenesis of energy metabolic turbulence with CVD25. With these mechanisms in mind we attempt to organize the related cells to establish MS models.

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