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Aspirin in stroke patients modifies the immunomodulatory interactions of marrow stromal cells and monocytes.
- Source :
-
Brain research [Brain Res] 2019 Oct 01; Vol. 1720, pp. 146298. Date of Electronic Publication: 2019 Jun 17. - Publication Year :
- 2019
-
Abstract
- Background and Objective: Most stroke patients are prescribed aspirin (ASA) to adjust blood coagulability. Marrow stromal cells (MSCs) are being tested in clinical trials for stroke patients who likely are prescribed aspirin. One of the principal mechanisms of action of MSCs and ASA is modulation of the inflammatory response, including those mediated by monocytes (Mo). Thus, here we tested if aspirin can modify anti-inflammatory properties of MSCs or Mo alone, and in combination.<br />Methods: Mo were isolated at 24 h of stroke onset from ischemic stroke patients with NIHSS ranging from 11 to 20 or from healthy controls. Human bone marrow-derived MSCs from healthy subjects were used at passage 3. Mo, MSCs, and MSCs-Mo co-cultures were exposed to ASA at clinically relevant doses. The secretome profile of inflammatory mediators was measured using Magpix multiplex cytokine array. Viability was measured using MTT assay. Linear mixed effect model was used for statistical analysis.<br />Results: Overall Mo from control subjects exposed to ASA showed increased secretion of IL-1RA, IL-8, MCP-1, and TNF-α and Mo from stroke patients showed greater release of IL-1RA and MCP-1. In MSCs-Mo co-cultures, ASA added to co-cultures of control Mo reduced fractalkine secretion while it increased the fractalkine secretion when added to Mo from stroke patients. In addition, in co-cultures independent of Mo origin, ASA reduced IL-6, IL-8, MCP-1, and TNF-α.<br />Conclusions: Aspirin in acute stroke patients may modulate the secretome profile of Mo and MSCs, thus potentially modulating immune and inflammatory responses associated with stroke. Our results suggest that stroke trials involving the use of intravenous MSCs should consider the effect of aspirin as a confounding factor.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Aged
Aspirin metabolism
Bone Marrow
Chemokine CCL2
Coculture Techniques
Cytokines
Female
Humans
Interleukin 1 Receptor Antagonist Protein
Male
Mesenchymal Stem Cells drug effects
Mesenchymal Stem Cells metabolism
Middle Aged
Monocytes drug effects
Monocytes metabolism
Stroke metabolism
Stromal Cells drug effects
Stromal Cells metabolism
Tumor Necrosis Factor-alpha
Aspirin therapeutic use
Immunomodulation drug effects
Stroke drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1720
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 31220426
- Full Text :
- https://doi.org/10.1016/j.brainres.2019.06.017