Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment
Impact of blocking CFTR function on antimicrobial activity of MSCs. To mimic CF cells, healthy bone marrow derived hMSCs were cultured in the presence and absence of CFTR blocker I-172 (10 μg/mL) without antibiotics for 24 hours. The hMSC supernatants were evaluated for the ability to impact Pseudomonas aeruginosa PA CFUs (a) and growth rate (b). Supernatants generated from CFTR deficient hMSCs were more inefficient at decreasing Pseudomonas aeruginosa CFUs ((b), ) and growth rate ((c), ) than hMSCs without CFTR activity blocked. Further, hMSCs with deficient CFTR activity had less ability to secrete LL-37 ((c), ) relative to controls. LL-37 production by bone marrow derived hMSCs is decreased when CFTR is blocked but can be increased by treating the cells with a variety of cytokine stimulators. hMSCs stimulated with cytokines IFNγ (100 ng/mL), IL-1B (50 ng/mL), and IL-12 (100 ng/mL) secreted significantly more LL-37 than unstimulated controls ((d), , different hMSC preparations).
|(a) Blocking CFTR function on Pseudomonas aeruginosa growth|
|(b) Growth kinetics|
|(c) Blocking CFTR function decreases LL-37 production|
|(d) hMSCs produce LL-37 in response to stimulation|