Cell-matrix interactions improve beta-cell survival and insulin secretion in three-dimensional culture

Tissue Eng Part A. 2008 Dec;14(12):1959-68. doi: 10.1089/ten.tea.2007.0238.

Abstract

Controlled matrix interactions were presented to pancreatic beta-cells in three-dimensional culture within poly(ethylene glycol) hydrogels. Dispersed MIN6 beta-cells were encapsulated in gel environments containing the following entrapped extracellular matrix (ECM) proteins: collagen type I, collagen type IV, fibrinogen, fibronectin, laminin, and vitronectin. In ECM-containing gels, beta-cell survival was significantly better than in gels without ECM over 10 days. Correspondingly, apoptosis in encapsulated beta-cells was less in the presence of each matrix protein, suggesting the ability of individual matrix interactions to prevent matrix signaling-related apoptosis (anoikis). MIN6 beta-cells cultured in gels containing collagen type IV or laminin secreted more insulin in response to glucose stimulation than beta-cells in all other experimental conditions. Variations in collagen type IV or laminin concentration between 10 microg/mL and 250 microg/mL did not affect insulin secretion. Finally, beta-cell function in hydrogels presenting both collagen type IV and laminin revealed synergistic interactions. With a total protein concentration of 100 microg/mL, three gel compositions of varying ratios of collagen type IV to laminin (25:75, 50:50, and 75:25) were tested. In the presence of 25 microg/mL of collagen type IV and 75 microg/mL of laminin, beta-cell insulin secretion was greater than with laminin or collagen type IV individually. These results demonstrate that specific, rationally designed extracellular environments promote isolated beta-cell survival and function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Communication* / drug effects
  • Cell Culture Techniques / methods*
  • Cell Survival / drug effects
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / metabolism
  • Glucose / pharmacology
  • Hydrogel, Polyethylene Glycol Dimethacrylate / metabolism
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Polyethylene Glycols / metabolism
  • Receptors, Cell Surface / metabolism

Substances

  • Extracellular Matrix Proteins
  • Insulin
  • Receptors, Cell Surface
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Polyethylene Glycols
  • Glucose