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Stem cells translational medicine2020; 9(7); 746-757; doi: 10.1002/sctm.19-0333

The mesenchymal stromal cell secretome impairs methicillin-resistant Staphylococcus aureus biofilms via cysteine protease activity in the equine model.

Abstract: Mesenchymal stromal cells (MSCs) from various species, such as humans, mice, and horses, were recently found to effectively inhibit the growth of various bacteria associated with chronic infections, such as nonhealing cutaneous wounds, via secretion of antimicrobial peptides. These MSC antimicrobial properties have primarily been studied in the context of the planktonic phenotype, and thus, information on the effects on bacteria in biofilms is largely lacking. The objectives of this study were to evaluate the in vitro efficacy of the MSC secretome against various biofilm-forming wound pathogens, including the methicillin-resistant Staphylococcus aureus (MRSA), and to explore the mechanisms that affect bacterial biofilms. To this end, we used equine MSCs, because the horse represents a physiologically relevant model for human wound healing and offers a readily translatable model for MSC therapies in humans. Our salient findings were that the equine MSC secretome inhibits biofilm formation and mature biofilms of various bacteria, such as Pseudomonas aeruginosa, S. aureus, and Staphylococcus epidermidis. Furthermore, we demonstrated that equine MSC secrete cysteine proteases that destabilize MRSA biofilms, thereby increasing the efficacy of antibiotics that were previously tolerated by the biofilms. In light of the rise of antibiotic-resistant bacterial strains as an increasing global health threat, our results provide the rationale for using the MSC secretome as a complementary treatment for bacterial skin infections in both humans and horses.
© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
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Publication Date: 2020-03-26 PubMed ID: 32216094PubMed Central: PMC7308642DOI: 10.1002/sctm.19-0333Google Scholar: Lookup
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  • Journal Article
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article presents a study of how the secretions, or “secretome,” of mesenchymal stromal cells (MSCs) can disrupt the biofilm of harmful bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), improving the effectiveness of antibiotics. The study utilizes equine MSCs as a model due to their similarities with human wound healing processes.

Research Objective and Context

  • The researchers aimed to understand how the MSC secretome impacts various bacteria that form biofilms, often causing persistent infections. The primary focus was the secretome’s impact on MRSA, a challenging bacteria responsible for several hard-to-treat infections in humans.
  • This research is significant in the face of increasing antibiotic resistance among bacterial strains across the world. It particularly seeks to understand if the MSC secretome can serve as a support to existing antibiotic treatments and thereby help in controlling infections more effectively.

Methodology

  • The researchers used MSCs from horses in their study. The choice of equine MSCs is based on their physiological similarities with humans, making horses a translatable model for human MSC therapies.
  • The study evaluated the in vitro efficacy of the MSC secretome against various pathogens known to form biofilms in wound infections.

Key Findings

  • It was observed that the secretome from equine MSCs can inhibit the formation of bacterial biofilms, including notoriously hard-to-treat ones like MRSA, Pseudomonas aeruginosa, and Staphylococcus epidermidis.
  • Another crucial discovery was that these MSCs secreted cysteine proteases. These proteins have the ability to destabilize biofilms formed by MRSA, thereby enhancing the effectiveness of previously ineffective antibiotics.

Implications of the Findings

  • The findings provide a scientific basis for the use of the MSC secretome as an additional method to treat bacterial skin infections in humans and horses. This approach could prove invaluable in the fight against antibiotic-resistant bacteria, which pose an escalating global health threat.

Cite This Article

APA
Marx C, Gardner S, Harman RM, Van de Walle GR. (2020). The mesenchymal stromal cell secretome impairs methicillin-resistant Staphylococcus aureus biofilms via cysteine protease activity in the equine model. Stem Cells Transl Med, 9(7), 746-757. https://doi.org/10.1002/sctm.19-0333

Publication

Stem cells translational medicine
ISSN: 2157-6580
NlmUniqueID: 101578022
Country: England
Language: English
Volume: 9
Issue: 7
Pages: 746-757

Researcher Affiliations

Marx, Charlotte
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Gardner, Sophia
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Harman, Rebecca M
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Van de Walle, Gerlinde R
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

MeSH Terms

  • Animals
  • Biofilms / drug effects
  • Cysteine Proteases / metabolism
  • Disease Models, Animal
  • Horses
  • Mesenchymal Stem Cells / drug effects
  • Methicillin-Resistant Staphylococcus aureus / drug effects

Conflict of Interest Statement

The authors declared no potential conflicts of interest.

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