31P magnetic resonance spectroscopy of endothelial cells grown in three-dimensional matrigel constructs as an enabling platform technology: II. The effect of anti-inflammatory drugs on phosphometabolite levels

Endothelium. Sep-Oct 2008;15(5-6):299-307. doi: 10.1080/10623320802487874.

Abstract

In the accompanying study, the authors presented phosphometabolite patterns of endothelial cells grown under three-dimensional (3D) conditions using (31)P magnetic resonance spectroscopy (MRS). Here the authors describe the effect of nonsteroidal anti-inflammatory drugs (NSAIDs), using this enabling platform technology, which is relevant for evaluating drug effects in tissue-engineered endothelial constructs. Treatment with indomethacin significantly changed the phosphometabolite fingerprint in this endothelial model, by, respectively, increasing (81%) and decreasing (42%) glycerophosphocholine (GPC) and phosphomonoesters (PM). Furthermore, a safer approach using a NSAID prodrug was also demonstrated in this study with a indomethacin phospholipid-derived prodrug (DP-155). Like the parental drug, DP-155 increased and decreased the levels of GPC and PM by 100% and 20%, respectively. These changes represent useful biomarkers to monitor NSAID effects on endothelized tissue-engineered constructs for the purpose of controlling endothelial cell survival and inflammation upon implantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Biochemistry / methods
  • Biological Assay / instrumentation
  • Biological Assay / methods
  • Bioreactors*
  • Cell Communication / physiology
  • Cell Line
  • Cell Line, Tumor
  • Coculture Techniques
  • Collagen / pharmacology
  • Drug Combinations
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Indomethacin / analogs & derivatives
  • Indomethacin / pharmacology
  • Inflammation / drug therapy
  • Laminin / pharmacology
  • Lipid Metabolism / drug effects
  • Magnetic Resonance Spectroscopy / methods*
  • Neuroglia / metabolism*
  • Organ Culture Techniques / methods
  • Phosphatidylcholines / pharmacology
  • Phospholipids / metabolism*
  • Phosphorus Isotopes / chemistry
  • Proteoglycans / pharmacology
  • Rats

Substances

  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • DP 155
  • Drug Combinations
  • Laminin
  • Phosphatidylcholines
  • Phospholipids
  • Phosphorus Isotopes
  • Proteoglycans
  • matrigel
  • Collagen
  • Indomethacin