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Sci Rep. 2017 Sep 21;7(1):12100. doi: 10.1038/s41598-017-12121-z.

Membrane particles generated from mesenchymal stromal cells modulate immune responses by selective targeting of pro-inflammatory monocytes.

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Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
Nephrology and Transplantation, Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
The Institute of Nanoscopy, Maastricht University, Maastricht, The Netherlands.
Nephrology and Transplantation, Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.


Mesenchymal stromal cells (MSC) are a promising therapy for immunological disorders. However, culture expanded MSC are large and get trapped in the capillary networks of the lungs after intravenous infusion, where they have a short survival time. Hypothetically, living cells are a risk for tumor formation. To reduce risks associated with MSC infusion and improve the distribution in the body, we generated membrane particles (MP) of MSC and MSC stimulated with IFN-γ (MPγ). Tracking analysis and electron microscopy indicated that the average size of MP was 120 nm, and they showed a round shape. MP exhibited ATPase, nucleotidase and esterase activity, indicating they are enzymatically active. MP and MPγ did not physically interact with T cells and had no effect on CD4+ and CD8+ T cells proliferation. However, MP and MPγ selectively bound to monocytes and decreased the frequency of pro-inflammatory CD14+CD16+ monocytes by induction of selective apoptosis. MP and MPγ increased the percentage of CD90 positive monocytes, and MPγ but not MP increased the percentage of anti-inflammatory PD-L1 monocytes. MPγ increased mRNA expression of PD-L1 in monocytes. These data demonstrate that MP have immunomodulatory properties and have potential as a novel cell-free therapy for treatment of immunological disorders.

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