Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation
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 th...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/108076 https://orcid.org/0000-0003-1937-9594 |
| _version_ | 1826188903667728384 |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science 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 |
| author_sort | Yang, Zijiang |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:06:48Z |
| format | Article |
| id | mit-1721.1/108076 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:06:48Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1080762022-09-23T10:59:37Z Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation 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 Massachusetts Institute of Technology. Institute for Medical Engineering & Science Koch Institute for Integrative Cancer Research at MIT Ng, Kelvin Songyu Tong, Zhixiang Lin, Charles Karp, Jeffrey 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. National Institutes of Health (U.S.) ((NIH) R01 grant HL095722) United States. Department of Defense (Grant #W81XWH-13-1-0305) 2017-04-12T18:02:42Z 2017-04-12T18:02:42Z 2016-07 2015-10 Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/108076 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. https://orcid.org/0000-0003-1937-9594 en_US http://dx.doi.org/10.1038/srep30263 Scientific Reports Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | 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 Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation |
| title | Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation |
| title_full | Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation |
| title_fullStr | Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation |
| title_full_unstemmed | Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation |
| title_short | Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation |
| title_sort | tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation |
| url | http://hdl.handle.net/1721.1/108076 https://orcid.org/0000-0003-1937-9594 |
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