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Nisin-preconditioned mesenchymal stem cells combatting nosocomial Pseudomonas infections
Sara Enayati1, Raheleh Halabian2, Parvaneh Saffarian1
1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Background:
Nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa are a considerable public health threat, requiring innovative therapeutic approaches.
Objectives:
This study explored preconditioning mesenchymal stem cells (MSCs) with the antimicrobial peptide Nisin to enhance their antibacterial properties while maintaining regenerative capacity.
Methods:
Human MSCs were preconditioned with varying concentrations of Nisin (0.1-1000 IU/mL) to determine an optimal dose. MSCs preconditioned with Nisin were characterized using microscopy, flow cytometry, gene expression analysis, and functional assays. The effects of preconditioning on the viability, phenotype, differentiation capacity, antimicrobial peptide expression, and antibacterial activity of MSCs against Pseudomonas aeruginosa were tested in vitro. The therapeutic efficacy was evaluated by topically applying conditioned media from Nisin-preconditioned versus control MSCs to infected wounds in a rat model, assessing bacterial burden, healing, host response, and survival.
Results:
An optimal Nisin dose of 500 IU/mL was identified, which increased MSC antibacterial gene expression and secretome activity without compromising viability or stemness. Nisin-preconditioned MSCs showed upregulated expression of LL37 and hepcidin. Conditioned media from Nisin-preconditioned MSCs exhibited about 4-fold more inhibition of P. aeruginosa growth compared to non-preconditioned MSCs. In the wound infection model, the secretome of Nisin-preconditioned MSCs suppressed bacterial load, accelerated wound closure, modulated inflammation, and improved survival compared to standard MSC treatments.
Conclusion:
This study explores the effect of preconditioning MSCs with the antimicrobial peptide Nisin on enhancing their antibacterial properties while maintaining regenerative capacity. Secreted factors from Nisin-preconditioned MSCs have the potential to attenuate infections and promote healing in vivo. The approach holds translational promise for managing antibiotic-resistant infections and warrants further development. Preconditioned MSCs with Nisin may offer innovative, multifaceted therapies for combating nosocomial pathogens and promoting tissue regeneration.
Insights
Preconditioning mesenchymal stem cells (MSCs) with Nisin enhances their ability to fight multidrug-resistant bacteria. This approach shows promise for treating infections and promoting wound healing.
Area of Science:
- Stem cell biology
- Antimicrobial research
- Regenerative medicine
Background:
- Nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa pose a significant public health challenge.
- Innovative therapeutic strategies are urgently needed to combat these resistant pathogens.
Purpose of the Study:
- To investigate the potential of preconditioning human mesenchymal stem cells (MSCs) with the antimicrobial peptide Nisin.
- To enhance MSCs' antibacterial properties against P. aeruginosa while preserving their regenerative capacity.
Main Methods:
- MSCs were preconditioned with varying Nisin concentrations to determine the optimal dose (500 IU/mL).
- Characterization involved microscopy, flow cytometry, gene expression, and functional assays.
- In vitro antibacterial activity against P. aeruginosa and in vivo efficacy in a rat wound infection model were assessed.
Main Results:
- Optimal Nisin preconditioning (500 IU/mL) upregulated MSCs' expression of LL37 and hepcidin, enhancing antibacterial secretome activity.
- Conditioned media from Nisin-preconditioned MSCs demonstrated a 4-fold increase in P. aeruginosa growth inhibition.
- In vivo, Nisin-preconditioned MSC secretome accelerated wound healing, reduced bacterial load, modulated inflammation, and improved survival.
Conclusions:
- Nisin preconditioning effectively enhances MSCs' antimicrobial capabilities without compromising their stemness or viability.
- Secreted factors from Nisin-preconditioned MSCs offer a promising therapeutic strategy for managing antibiotic-resistant infections and promoting tissue regeneration.
- This approach presents a potential innovative, multifaceted therapy for nosocomial pathogens and tissue repair.
