title: Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment.
abstract: Cystic fibrosis (CF) is a genetic disease in which the battle between pulmonary infection and inflammation becomes the major cause of morbidity and mortality. We have previously shown that human MSCs (hMSCs) decrease inflammation and infection in the in vivo murine model of CF. The studies in this paper focus on the specificity of the hMSC antimicrobial effectiveness using Pseudomonas aeruginosa (gram negative bacteria) and Staphylococcus aureus (gram positive bacteria). Our studies show that hMSCs secrete bioactive molecules which are antimicrobial in vitro against Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumonia, impacting the rate of bacterial growth and transition into colony forming units regardless of the pathogen. Further, we show that the hMSCs have the capacity to enhance antibiotic sensitivity, improving the capacity to kill bacteria. We present data which suggests that the antimicrobial effectiveness is associated with the capacity to slow bacterial growth and the ability of the hMSCs to secrete the antimicrobial peptide LL-37. Lastly, our studies demonstrate that the tissue origin of the hMSCs (bone marrow or adipose tissue derived), the presence of functional cystic fibrosis transmembrane conductance regulator (CFTR: human, Cftr: mouse) activity, and response to effector cytokines can impact both hMSC phenotype and antimicrobial potency and efficacy. These studies demonstrate, the unique capacity of the hMSCs to manage different pathogens and the significance of their phenotype in both the antimicrobial and antibiotic enhancing activities.
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA; National Center of Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Morgan T
authors.initials: MT
authors.lastname: Sutton
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: David
authors.initials: D
authors.lastname: Fletcher
authors.affiliation: School of Dentistry, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Ghosh
authors.affiliation: School of Dentistry, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Weinberg
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Rolf
authors.initials: R
authors.lastname: van Heeckeren
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Sukhmani
authors.initials: S
authors.lastname: Kaur
authors.affiliation: Department of Urology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Zhina
authors.initials: Z
authors.lastname: Sadeghi
authors.affiliation: Department of Urology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Adonis
authors.initials: A
authors.lastname: Hijaz
authors.affiliation: National Center of Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Cancer Biology, Case Western Reserve University, Cleveland, OH 44106, USA; CTSC Cell Therapy Laboratory, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Reese
authors.affiliation: National Center of Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Cancer Biology, Case Western Reserve University, Cleveland, OH 44106, USA; CTSC Cell Therapy Laboratory, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: National Center of Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Biology, Case Western Reserve University, Cleveland, OH 44106, USA; Skeletal Research Center, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Lennon
authors.affiliation: National Center of Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Biology, Case Western Reserve University, Cleveland, OH 44106, USA; Skeletal Research Center, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Arnold I
authors.initials: AI
authors.lastname: Caplan
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA; National Center of Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Bonfield