Accession Number : ADA620317


Title :   Soluble Factors from Biofilms of Wound Pathogens Modulate Human Bone Marrow-derived Stromal Cell Differentiation, Migration, Angiogenesis, and Cytokine Secretion


Descriptive Note : Journal article


Corporate Author : ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX


Personal Author(s) : Ward, Catherine L ; Sanchez, Jr, Carlos J ; Pollot, Beth E ; Romano, Desiree R ; Hardy, Sharanda K ; Becerra, Sandra C ; Rathbone, Christopher R ; Wenke, Joseph C


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a620317.pdf


Report Date : 28 Mar 2015


Pagination or Media Count : 15


Abstract : 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. 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. 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 t he context of infection may have a limited therapeutic effect.


Descriptors :   *CYTOKINES , *INFECTIOUS DISEASES , *PATHOGENIC MICROORGANISMS , *WOUNDS AND INJURIES , ANGIOGENESIS , BONE MARROW , CELLS(BIOLOGY) , CONNECTIVE TISSUE , EMBRYOS , EXPOSURE(PHYSIOLOGY) , HEALING , HOSTS(BIOLOGY) , HUMAN BODY , IMMUNITY , IN VITRO ANALYSIS , INFLAMMATION , ORGANIC MATERIALS , POLYSACCHARIDES , PSEUDOMONAS AERUGINOSA , RESPONSE(BIOLOGY) , SOLUBILITY , STAPHYLOCOCCUS AUREUS , THERAPY , VIABILITY


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research
      Microbiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE