Aspirin in stroke patients modifies the immunomodulatory interactions of marrow stromal cells and monocytes

• Published in: Brain research Vol. 1720; p. 146298
• Main Authors: Satani, Nikunj, Giridhar, Kaavya, Cai, Chunyan, Wewior, Natalia, Norris, Dominique D., Olson, Scott D., Aronowski, Jaroslaw, Savitz, Sean I.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2019
• Subjects: Cell interactions; Fractalkine; IL-1RA; Immunomodulation; Mesenchymal stromal cells; Monocytes; Mesenchymal stromal cells; Monocytes; Fractalkine; IL-1RA; Cell interactions; Immunomodulation
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2019.06.017

[Display omitted] •Aspirin changes the secretome from monocytes of stroke patients.•MSCs have differential effect on monocytes in the presence of aspirin.•These effects should be considered when conducting clinical trials of MSCs in stroke. 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. 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. 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. 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.