title: Soluble factors from biofilms of wound pathogens modulate human bone marrow-derived stromal cell differentiation, migration, angiogenesis, and cytokine secretion.
abstract: BACKGROUND
  Chronic, non-healing wounds are often characterized by the persistence of bacteria within biofilms - aggregations of cells encased within a self-produced polysaccharide matrix. Biofilm bacteria exhibit unique characteristics from planktonic, or culture-grown, bacterial phenotype, including diminished responses to antimicrobial therapy and persistence against host immune responses. Mesenchymal stromal cells (MSCs) are host cells characterized by their multifunctional ability to undergo differentiation into multiple cell types and modulation of host-immune responses by secreting factors that promote wound healing. While these characteristics make MSCs an attractive therapeutic for wounds, these pro-healing activities may be differentially influenced in the context of an infection (i.e., biofilm related infections) within chronic wounds. Herein, we evaluated the effect of soluble factors derived from biofilms of clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa on the viability, differentiation, and paracrine activity of human MSCs to evaluate the influence of biofilms on MSC activity in vitro.
  
  
  RESULTS
  Exposure of MSCs to biofilm-conditioned medias of S. aureus and P. aeruginosa resulted in reductions in cell viability, in part due to activation of apoptosis. Similarly, exposure to soluble factors from biofilms was also observed to diminish the migration ability of cells and to hinder multi-lineage differentiation of MSCs. In contrast to these findings, exposure of MSCs to soluble factors from biofilms resulted in significant increases in the release of paracrine factors involved in inflammation and wound healing.
  
  
  CONCLUSIONS
  Collectively, these findings demonstrate that factors produced by biofilms can negatively impact the intrinsic properties of MSCs, in particular limiting the migratory and differentiation capacity of MSCs. Consequently, these studies suggest use/application of stem-cell therapies in the context of infection may have a limited therapeutic effect.
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, USA. catherine.l.ward.vol@mail.mil.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Ward
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, USA. carlos.j.sanchez47.vol@mail.mil.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Sanchez
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, USA. bepollot@gmail.com.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Pollot
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, USA. desiree.r.romano@gmail.com.
authors.forename: Desiree R
authors.initials: DR
authors.lastname: Romano
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, USA. sharanda.k.hardy.ctr@mail.mil.
authors.forename: Sharanda K
authors.initials: SK
authors.lastname: Hardy
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, USA. sandra.c.beccera.ctr@mail.mil.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Becerra
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, USA. chris.r.rathbone.civ@mail.mil.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Rathbone
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, USA. joseph.c.wenke.civ@mail.mil.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wenke
mesh_terms: D018441:Biofilms / Q000254:growth & development; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009930:Organic Chemicals / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology; D014946:Wound Infection / Q000382:microbiology*
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D009930:Organic Chemicals