Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation
Author(s)
Yang, Zijiang; Concannon, John; Seyb, Kathleen; Mortensen, Luke J.; Ranganath, Sudhir; Gu, Fangqi; Levy, Oren; Martyn, Keir; Zhao, Weian; Glicksman, Marcie A.; Ng, Kelvin Songyu; Tong, Zhixiang; Lin, Charles; Karp, Jeffrey Michael; ... Show more Show less
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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.
Date issued
2016-07Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Koch Institute for Integrative Cancer Research at MITJournal
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
ISSN
2045-2322