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.
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.
Ringel
I
I
Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Lecht
S
S
Sterin
M
M
Lelkes
P I
PI
Lazarovici
P
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001671:Biochemistry / Q000379:methods; D001681:Biological Assay / Q000295:instrumentation / Q000379:methods; D019149:Bioreactors; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D007213:Indomethacin / Q000031:analogs & derivatives / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy; D007797:Laminin / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009457:Neuroglia / Q000378:metabolism*; D009924:Organ Culture Techniques / Q000379:methods; D010713:Phosphatidylcholines / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D010759:Phosphorus Isotopes / Q000737:chemistry; D011509:Proteoglycans / Q000494:pharmacology; D051381:Rats
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; C514017:DP 155; D004338:Drug Combinations; D007797:Laminin; D010713:Phosphatidylcholines; D010743:Phospholipids; D010759:Phosphorus Isotopes; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D007213:Indomethacin