Effect of MSC treatment on LPS-induced inflammation, emphysema and atherosclerosis in E3L mice

Background: COPD patients have an increased risk of cardiovascular diseases (CVD), which may be linked through systemic inflammation triggered by smoke and microbial exposure. Recent studies show the promising antiinflammatory and regenerative effects of mesenchymal stromal cells (MSC). Since current treatment of COPD with CVD is suboptimal, we examined the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS)-induced inflammation, emphysema and diet-induced atherosclerosis in hyperlipidemic APOE*3-Leiden ( E3L ) mice. Methods: Western-type diet-fed E3L mice were intranasally instilled (2x/wk) with PBS or 10 µg LPS for 1 week (acute study) or 20 weeks (chronic study). Mice received PBS or 0.5x10 6 MSC intravenously twice after the first LPS instillation (acute) or in week 14, 16, 18 and 20 (1x/wk; chronic). After sacrifice, inflammatory parameters were measured in bronchoalveolar lavage (BAL) and lungs. In the chronic study, emphysema, inflammation and atherosclerosis were also analysed. Results: In the acute study, intranasal LPS induced a systemic IL-6 response on day 3 (1370 vs. 80 pg/mL in PBS; p Conclusion: This study shows that whereas MSC inhibit intranasal LPS-induced pulmonary cell influx and systemic inflammation in an acute setting, MSC did not modify emphysema and atherosclerosis development in a chronic study.