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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.

Author information

1
Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
2
Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
3
Nephrology and Transplantation, Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
4
The Institute of Nanoscopy, Maastricht University, Maastricht, The Netherlands.
5
Nephrology and Transplantation, Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. m.hoogduijn@erasmusmc.nl.

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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