A cell-based drug delivery platform for treating central nervous system inflammation.
Levy O, Rothhammer V, Mascanfroni I, Tong Z, Kuai R, De Biasio M, Wang Q, Majid T, Perrault C, Yeste A, Kenison JE, Safaee H, Musabeyezu J, Heinelt M, Milton Y, Kuang H, Lan H, Siders W, Multon MC, Rothblatt J, Massadeh S, Alaamery M, Alhasan AH, Quintana FJ, Karp JM (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 99
Pages Range: 663-671
Journal Issue: 5
DOI: 10.1007/s00109-020-02003-9
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. KEY MESSAGES: MSCs can spontaneously take up the ATP-competitive kinase inhibitor Ro-31-8425. Ro-31-8425-loaded MSCs gradually release Ro-31-8425 and exhibit sustained suppression of T cells. Ro-31-8425-loaded MSCs have more sustained serum levels of Ro-31-8425 than free Ro-31-8425. Ro-31-8425-loaded MSCs are more effective than MSCs and free Ro-31-8425 for EAE therapy.
Authors with CRIS profile
Involved external institutions
Sanofi-Aventis Groupe
France (FR)
Harvard University
United States (USA) (US)
Sanofi Genzyme
United States (USA) (US)
National Guard Health Affairs
Saudi Arabia (SA)
King Abdulaziz City for Science and Technology
Saudi Arabia (SA)
France (FR)
Harvard University
United States (USA) (US)
Sanofi Genzyme
United States (USA) (US)
National Guard Health Affairs
Saudi Arabia (SA)
King Abdulaziz City for Science and Technology
Saudi Arabia (SA)
How to cite
APA:
Levy, O., Rothhammer, V., Mascanfroni, I., Tong, Z., Kuai, R., De Biasio, M.,... Karp, J.M. (2021). A cell-based drug delivery platform for treating central nervous system inflammation. Journal of Molecular Medicine, 99(5), 663-671. https://dx.doi.org/10.1007/s00109-020-02003-9
MLA:
Levy, Oren, et al. "A cell-based drug delivery platform for treating central nervous system inflammation." Journal of Molecular Medicine 99.5 (2021): 663-671.
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