Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment

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 p...

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Main Authors: Morgan T. Sutton, David Fletcher, Santosh K. Ghosh, Aaron Weinberg, Rolf van Heeckeren, Sukhmani Kaur, Zhina Sadeghi, Adonis Hijaz, Jane Reese, Hillard M. Lazarus, Donald P. Lennon, Arnold I. Caplan, Tracey L. Bonfield
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/5303048
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author Morgan T. Sutton
David Fletcher
Santosh K. Ghosh
Aaron Weinberg
Rolf van Heeckeren
Sukhmani Kaur
Zhina Sadeghi
Adonis Hijaz
Jane Reese
Hillard M. Lazarus
Donald P. Lennon
Arnold I. Caplan
Tracey L. Bonfield
author_facet Morgan T. Sutton
David Fletcher
Santosh K. Ghosh
Aaron Weinberg
Rolf van Heeckeren
Sukhmani Kaur
Zhina Sadeghi
Adonis Hijaz
Jane Reese
Hillard M. Lazarus
Donald P. Lennon
Arnold I. Caplan
Tracey L. Bonfield
author_sort Morgan T. Sutton
collection DOAJ
description 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.
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spelling doaj-art-4c5ba932ffc54167966f019169fbc28a2025-02-03T06:08:23ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/53030485303048Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and TreatmentMorgan T. Sutton0David Fletcher1Santosh K. Ghosh2Aaron Weinberg3Rolf van Heeckeren4Sukhmani Kaur5Zhina Sadeghi6Adonis Hijaz7Jane Reese8Hillard M. Lazarus9Donald P. Lennon10Arnold I. Caplan11Tracey L. Bonfield12Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USASchool of Dentistry, Case Western Reserve University, Cleveland, OH 44106, USASchool of Dentistry, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Urology, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Urology, Case Western Reserve University, Cleveland, OH 44106, USANational Center of Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USANational Center of Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USANational Center of Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USANational Center of Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USACystic 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.http://dx.doi.org/10.1155/2016/5303048
spellingShingle Morgan T. Sutton
David Fletcher
Santosh K. Ghosh
Aaron Weinberg
Rolf van Heeckeren
Sukhmani Kaur
Zhina Sadeghi
Adonis Hijaz
Jane Reese
Hillard M. Lazarus
Donald P. Lennon
Arnold I. Caplan
Tracey L. Bonfield
Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment
Stem Cells International
title Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment
title_full Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment
title_fullStr Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment
title_full_unstemmed Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment
title_short Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment
title_sort antimicrobial properties of mesenchymal stem cells therapeutic potential for cystic fibrosis infection and treatment
url http://dx.doi.org/10.1155/2016/5303048
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