Functional differences between healthy and diabetic endothelial cells on topographical cues

Biomaterials. 2018 Jan;153:70-84. doi: 10.1016/j.biomaterials.2017.10.037. Epub 2017 Oct 25.

Abstract

The endothelial lining of blood vessels is severely affected in type II diabetes. Yet, there is still a paucity on the use of diabetic endothelial cells for study and assessment of implantable devices targeting vascular disease. This critically impairs our ability to determine appropriate topographical cues to be included in implantable devices that can be used to maintain or improve endothelial cell function in vivo. Here, the functional responses of healthy and diabetic human coronary arterial endothelial cells were studied and observed to differ depending on topography. Gratings (2 μm) maintained normal endothelial functions such as adhesiveness, angiogenic capacity and cell-cell junction formation, and reduced immunogenicity of healthy cells. However, a significant and consistent effect was not observed in diabetic cells. Instead, diabetic endothelial cells cultured on the perpendicularly aligned multi-scale hierarchical gratings (250 nm gratings on 2 μm gratings) drastically reduced the uptake of oxidized low-density lipoprotein, decreased immune activation, and accelerated cell migration. Concave microlens (1.8 μm diameter) topography was additionally observed to overwhelmingly deteriorate diabetic endothelial cell function. The results of this study support a new paradigm and approach in the design and testing of implantable devices and biomedical interventions for diabetic patients.

Keywords: Cell therapy; Disease cells; Donor-derived cells; Endothelialization; Mechanobiology; Tissue engineering.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Cell Shape
  • Cells, Cultured
  • Coronary Vessels / metabolism*
  • Coronary Vessels / pathology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism*
  • Endothelial Cells / physiology
  • Female
  • Fluorescent Dyes / chemistry
  • Gene Expression
  • Humans
  • Lipoproteins, LDL / metabolism
  • Male
  • Middle Aged
  • Neovascularization, Physiologic

Substances

  • Fluorescent Dyes
  • Lipoproteins, LDL
  • oxidized low density lipoprotein