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

Membrane particles generated from mesenchymal stromal cells modulate immune responses by selective targeting of pro-inflammatory monocytes.
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Gonçalves FDC, Luk F, Korevaar SS, Bouzid R, Paz AH, López-Iglesias C, Baan CC, Merino A, Hoogduijn MJ,


Gonçalves FDC, Luk F, Korevaar SS, Bouzid R, Paz AH, López-Iglesias C, Baan CC, Merino A, Hoogduijn MJ, (click to view)

Gonçalves FDC, Luk F, Korevaar SS, Bouzid R, Paz AH, López-Iglesias C, Baan CC, Merino A, Hoogduijn MJ,

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Scientific reports 2017 09 217(1) 12100 doi 10.1038/s41598-017-12121-z
Abstract

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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