A cell-based drug delivery platform for treating central nervous system inflammation
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Author(s)
Levy, Oren
Rothhammer, Veit
Mascanfroni, Ivan
Tong, Zhixiang
Kuai, Rui
De Biasio, Michael
Wang, Qingping
Majid, Tahir
Perrault, Christelle
Yeste, Ada
Date Issued
January 2021
Journal
Journal of Molecular Medicine
Publisher
Springer Science and Business Media LLC
Citation
Levy, Oren et al. "A cell-based drug delivery platform for treating central nervous system inflammation." Journal of Molecular Medicine 99, 5 (January 2021): 663–671. © 2021 Springer-Verlag GmbH Germany, part of Springer Nature
Version
Author's final manuscript
Abstract
Mesenchymal stem cells (MSCs) are promising candidates for the development of cell-based drug delivery systems for autoimmune inflammatory diseases, such as multiple sclerosis (MS). Here, we investigated the effect of Ro-31-8425, an ATP-competitive kinase inhibitor, on the therapeutic properties of MSCs. Upon a simple pretreatment procedure, MSCs spontaneously took up and then gradually released significant amounts of Ro-31-8425. Ro-31-8425 (free or released by MSCs) suppressed the proliferation of CD4+ T cells in vitro following polyclonal and antigen-specific stimulation. Systemic administration of Ro-31-8425-loaded MSCs ameliorated the clinical course of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, displaying a stronger suppressive effect on EAE than control MSCs or free Ro-31-8425. Ro-31-8425-MSC administration resulted in sustained levels of Ro-31-8425 in the serum of EAE mice, modulating immune cell trafficking and the autoimmune response during EAE. Collectively, these results identify MSC-based drug delivery as a potential therapeutic strategy for the treatment of autoimmune diseases.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Broad Institute of MIT and Harvard
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1007/s00109-020-02003-9
