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

Fabiany da C. Goncalves, Franka Luk, Sander S. Korevaar, Rachid Bouzid, Ana H. Paz, Carmen Lopez-Iglesias, Carla C. Baan, Ana Merino, Martin J. Hoogduijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

45 Citations (Web of Science)

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-gamma (MP gamma). 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 MP gamma did not physically interact with T cells and had no effect on CD4(+) and CD8(+) T cells proliferation. However, MP and MP gamma selectively bound to monocytes and decreased the frequency of pro-inflammatory CD14(+) CD16(+) monocytes by induction of selective apoptosis. MP and MP gamma increased the percentage of CD90 positive monocytes, and MP gamma but not MP increased the percentage of antiinflammatory PD-L1 monocytes. MP gamma 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.

Original languageEnglish
Article number12100
Number of pages13
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 21 Sep 2017

Keywords

  • STEM-CELLS
  • IMMUNOMODULATORY CAPACITY
  • INTERFERON-GAMMA
  • T-CELLS
  • DIFFERENTIATION
  • CD73
  • TRANSPLANTATION
  • IMMUNOTHERAPY
  • INFLAMMATION
  • EXOSOMES

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