IL-10 OVEREXPRESSING HUMAN UMBILICAL CORD MESENCHYMAL STROMAL/STEM CELLS (IL-10 UC-MSCs) IMPROVE RECOVERY AND REDUCE BACTERIAL BURDEN IN RODENT E. COLI PNEUMONIA MORE EFFECTIVELY THAN REGULAR UC-MSCs
CCCF ePoster library. Jerkic M. Oct 4, 2017; 198197; 91 Disclosure(s): Nothing to declare
Dr. Mirjana Jerkic
Dr. Mirjana Jerkic
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IL-10 OVEREXPRESSING HUMAN UMBILICAL CORD MESENCHYMAL STROMAL/STEM CELLS (IL-10 UC-MSCs) IMPROVE RECOVERY AND REDUCE BACTERIAL BURDEN IN RODENT E. COLI PNEUMONIA MORE EFFECTIVELY THAN REGULAR UC-MSCs

Jerkic, Mirjana 1; Ormesher, Lindsay 1; Goyal, Sakshi 1; Gagnon, Stephane 1; Rabani, Razieh 1; Curley, Gerard 1; Laffey, John1

Department of Anaesthesia, Keenan Research Centre of St. Michael’s Hospital, University of Toronto, Toronto, Canada 


Introduction: Acute respiratory distress syndrome (ARDS) is characterized by widespread injury of the alveolar-capillary membrane and loss of aerated lung tissue, and has a hospital mortality of over 40% (Bellani et al, 2016). There are no pharmacological therapies for ARDS; hence the treatment is entirely supportive. Mesenchymal Stromal/Stem Cells (MSCs) isolated from bone marrow or umbilical cord (UC) confer high potential applicability for ARDS (Curley & Laffey, 2013, Gupta et al. 2012, Curley et al, 2012 & 2017). ARDS is characterized by dysregulated inflammation, inappropriate pulmonary immune cell accumulation and elevated release of pro-inflammatory cytokines. Interleukin-10 plays a key role in the regulation of the host inflammatory response to infection.
Objective: We wished to determine the potential of increasing the efficacy of UC-MSCs by overexpressing IL-10, in a rodent pneumonia ARDS model.
Methods: UC-MSCs overexpression of IL10 was established through adenoviral transduction. ARDS was induced in rats by intra-tracheal E. coli instillation (8-9x109 CFU/kg), and regular (naïve) or IL-10 UC-MSCs (both obtained from Tissue Regeneration Therapeutics, Toronto) were given to the rats by tail vein 1h after ARDS induction (10x10^6/kg) while control group received vehicle (PBS). Survival, pulmonary function, inflammation and bacterial clearance were assessed 48 hours later. Lung structural analysis was also performed while the effect of both regular & IL-10 UC-MSCs on macrophage (Mɸ) phagocytosis was tested in vitro using FITC labeled Zymosan particles.
Results: IL-10 UC-MSCs were more effective than regular UC-MSCs in reducing lung bacterial burden in ARDS rats. Lungs were macroscopically less injured and alveolar airspace was significantly increased in rats treated with IL-10 compared to regular UC-MSCs. Lung inflammatory cell infiltration and neutrophil counts were lower in broncho-alveolar lavage (BAL) in both IL-10 and regular UC-MSCs treated groups compared with vehicle treated animals. The percentage of neutrophils was reduced while macrophage differential count was increased in BAL of IL-10 UC-MSCs-treated group only (30.7+/-8.9%) compared to both vehicle-treated (19.8+/-11.2%) and regular UC-MSCs-treated group (24.1+/-10.6%). Our in vitro data have shown that both regular and IL-10 UC-MSCs increase ability of Mɸ to phagocytose while phagocytic index is furthermore increased by IL-10 UC-MSCs.
Conclusions: IL-10 overexpressing UC-MSCs were more effective than naïve UC-MSCs in our rodent E. coli pneumonia model. This enhanced effect of IL-10 UC-MSCs may be mediated via enhanced macrophage function. IL-10 overexpressing UC-MSCs may represent an attractive option for clinical trials in ARDS. 

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