The effect of extracellular matrix components on the preservation of human islet function in vitro

Biomaterials. 2010 Mar;31(7):1676-82. doi: 10.1016/j.biomaterials.2009.11.057. Epub 2009 Dec 16.

Abstract

Human islet isolation leads to the loss of the ECM basement membrane which contributes to eventual apoptosis in vitro. The reestablishment of this environment is vital in understanding the mechanism of islet interaction with its surroundings in order to arrive at conditions favourable to islet culture in vitro. In this study, we investigated the effects of the main ECM components collagen I and IV, fibronectin, and laminin on human islet adhesion, survival, and functionality. Results have provided insight into integrin-mediated effects and behaviour. Collagen I/IV and fibronectin induced adhesion, while fibronectin was the only ECM protein capable of maintaining islet structural integrity and insulin content distribution. Furthermore, islet phenotype was eventually lost, but insulin gene expression was highest in islets cultured on collagen I and IV. However, insulin release was highest on fibronectin, along with a decrease in SUR1 expression, while glucose metabolism, along with GLUT2 and GCK expression, was highest on collagen I and IV surfaces. These findings provide a basis for the future establishment of a modified three-dimensional construct for the culture of human pancreatic islets in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesiveness / drug effects
  • Biological Assay
  • Cell Survival / drug effects
  • Cells, Cultured
  • Coated Materials, Biocompatible / pharmacology
  • Extracellular Matrix Proteins / pharmacology*
  • Gene Expression Regulation / drug effects
  • Glucose / pharmacology
  • Humans
  • Immunohistochemistry
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / physiology*
  • Islets of Langerhans / ultrastructure
  • Microscopy, Atomic Force
  • Surface Properties / drug effects

Substances

  • Coated Materials, Biocompatible
  • Extracellular Matrix Proteins
  • Glucose