Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation

Sci Rep. 2016 Jul 26;6:30263. doi: 10.1038/srep30263.

Abstract

Pre-treatment or priming of mesenchymal stem cells (MSC) prior to transplantation can significantly augment the immunosuppressive effect of MSC-based therapies. In this study, we screened a library of 1402 FDA-approved bioactive compounds to prime MSC. We identified tetrandrine as a potential hit that activates the secretion of prostaglandin E2 (PGE2), a potent immunosuppressive agent, by MSC. Tetrandrine increased MSC PGE2 secretion through the NF-κB/COX-2 signaling pathway. When co-cultured with mouse macrophages (RAW264.7), tetrandrine-primed MSC attenuated the level of TNF-α secreted by RAW264.7. Furthermore, systemic transplantation of primed MSC into a mouse ear skin inflammation model significantly reduced the level of TNF-α in the inflamed ear, compared to unprimed cells. Screening of small molecules to pre-condition cells prior to transplantation represents a promising strategy to boost the therapeutic potential of cell therapy.

Publication types

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

MeSH terms

  • Animals
  • Benzylisoquinolines / pharmacology*
  • Cyclooxygenase 2 / immunology
  • Humans
  • Immunomodulation / drug effects
  • Immunosuppressive Agents / pharmacology*
  • Mass Screening
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / immunology
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / immunology
  • RAW 264.7 Cells
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Small Molecule Libraries

Substances

  • Benzylisoquinolines
  • Immunosuppressive Agents
  • NF-kappa B
  • Small Molecule Libraries
  • tetrandrine
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2