Abstract WP267: Adipose Stem Cells Restore Alveolar Macrophage and Monocyte Dynamics after Ischemic Stroke

Abstract

Background: Pneumonia is a complication in stroke patients. Resident alveolar macrophages (AMΦs) are the predominant cell type in the alveolar space with a slow turn-over rate maintained by monocytes (Mo). Distinct macrophage (MΦ) populations have protective (tissue homeostasis) or pathogenic roles (inflammation), the balance of which might predispose to pneumonia. The lungs are the first pass filter for the intravenous administration of various cell therapies but the effects of cell therapies within the lungs are largely unknown. The objective of this study was to determine the dynamics of AMΦs subpopulations and Mo in ischemic stroke and investigate the effects of acute adipose stem cells (ASC) on these alveolar cell populations. Methods: C57 mice were subjected to 60 min ischemia by the intraluminal filament model. ASCs, harvested from donor mice adipose tissue, were injected IV 4h after ischemia. BAL was collected 72h after ischemia and processed for flow cytometry. Macrophages and monocyte cells were assessed based on CD45, CD11b and CD11c expression. For lung inflammation, BAL cytospin slides and slides stained for HE and Toluidine blue were processed at 24h, 48h, and 72h. Results: There were no significant differences in lung pathology and in BAL cell differentiation between sham and stroke animals. Total AMΦ cell count in BAL did not change acutely (days 1 to 3) after stroke when compared with sham or naïve animals. Compared to naive animals, vehicle group had a significant decrease in the Mo population (CD45 pos / CD 11b high /CD 11c neg/low ; 11.29% ± 9.5; 1.5% ± 0.9; 4.47% ± 4.0) and a decreasing trend in activated AMΦs subpopulation (CD45 pos / CD 11b pos /CD 11c high ). These changes appeared to be driven by CD86 rather than CD206 AMΦ and were not observed in ASC treated animals. Conclusion: We identified heterogeneity and differential responses in AMΦ/monocyte populations in the lung after ischemic stroke. Our results suggest that ASC treatment might prevent the decrease in lung monocyte/activated AMΦ populations, thus preserving the beneficial host defense mechanisms against post stroke pneumonia. This study suggests new target candidates within the lung to attenuate post stroke pneumonia and possible new mechanisms for cell therapy in stroke.