Abstract
BackgroundChronic, 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.ResultsExposure 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.ConclusionsCollectively, 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0412-x) contains supplementary material, which is available to authorized users.
Highlights
Chronic, non-healing wounds are often characterized by the persistence of bacteria within biofilms - aggregations of cells encased within a self-produced polysaccharide matrix
Given the importance of bacterial biofilms in the development of chronic wounds, the ability of these communities to inhibit wound healing, and the likely interactions with host cells such as Mesenchymal stromal cells (MSCs), we evaluated the effect of soluble factors from biofilms of clinical isolates of S. aureus and P. aeruginosa on the viability, differentiation, and paracrine activity of human bone marrow stromal cells in vitro
Soluble factors from biofilms reduce the viability of human bone marrow stromal cells (hBMSCs), in part due to the activation of apoptosis Initial screening of the effect of soluble factors of biofilms on cell viability, was performed by exposing hBMSCs to biofilm factors of S. aureus and P. aeruginosa at increasing concentrations (0, 5, 10, 25, 50, 75, and 100%) in cell growth media for 24 hours
Summary
Non-healing wounds are often characterized by the persistence of bacteria within biofilms - aggregations of cells encased within a self-produced polysaccharide matrix. 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. Recent studies evaluating the biodiversity within various types of chronic wounds demonstrated the presence of multiple species of bacteria, including Staphylococcus aureus, Pseudomonas. Studies evaluating interactions between biofilm communities and cells involved in wound healing will be central to further our understanding of how these processes may be perturbed during infection
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