Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation
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Tetradrine identified.pdf
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Author(s)
Yang, Zijiang
Concannon, John
Seyb, Kathleen
Mortensen, Luke J.
Ranganath, Sudhir
Gu, Fangqi
Levy, Oren
Martyn, Keir
Zhao, Weian
Glicksman, Marcie A.
Date Issued
July 2016
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Yang, Zijiang, John Concannon, Kelvin S. Ng, Kathleen Seyb, Luke J. Mortensen, Sudhir Ranganath, Fangqi Gu, et al. “Tetrandrine Identified in a Small Molecule Screen to Activate Mesenchymal Stem Cells for Enhanced Immunomodulation.” Scientific Reports 6 (July 26, 2016): 30263.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/srep30263
