PDF(Pubmed)
Abstract：
UNASSIGNED: Nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa are a considerable public health threat, requiring innovative therapeutic approaches.
UNASSIGNED: This study explored preconditioning mesenchymal stem cells (MSCs) with the antimicrobial peptide Nisin to enhance their antibacterial properties while maintaining regenerative capacity.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: This study explored preconditioning mesenchymal stem cells (MSCs) with the antimicrobial peptide Nisin to enhance their antibacterial properties while maintaining regenerative capacity.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■多重耐药铜绿假单胞菌引起的医院感染是相当大的公共卫生威胁，需要创新的治疗方法。
■这项研究探索了用抗菌肽Nisin预处理间充质干细胞（MSC）以增强其抗菌性能，同时保持再生能力。
用不同浓度的Nisin(0.1-1000IU/mL)预调节人MSC以确定最佳剂量。用Nisin预处理的MSCs使用显微镜进行表征，流式细胞术,基因表达分析,和功能测定。预处理对生存能力的影响，表型,分化能力，抗菌肽表达，并对MSCs的体外抗菌活性进行了检测。通过在大鼠模型中将来自Nisin预调理与对照MSC的条件培养基局部应用于感染的伤口来评估治疗功效。评估细菌负担，愈合，主机响应,和生存。
■确定了500IU/mL的最佳Nisin剂量，其增加MSC抗菌基因表达和分泌组活性而不损害生存力或干性。Nisin预处理的MSC显示LL37和铁调素的表达上调。与非预处理的MSC相比,来自Nisin预处理的MSC的条件培养基表现出对铜绿假单胞菌生长的约4倍的抑制。在伤口感染模型中,Nisin预处理MSCs的分泌组抑制细菌负荷，加速伤口闭合,调制炎症，与标准MSC治疗相比，存活率提高。
■这项研究探索了用抗菌肽Nisin预处理MSC对增强其抗菌性能同时保持再生能力的作用。来自Nisin预处理的MSC的分泌因子具有减弱感染和促进体内愈合的潜力。该方法为管理抗生素耐药性感染提供了转化的希望，并值得进一步发展。预处理MSC与Nisin可以提供创新，对抗医院病原体和促进组织再生的多方面疗法。
■这项研究探索了用抗菌肽Nisin预处理间充质干细胞（MSC）以增强其抗菌性能，同时保持再生能力。
用不同浓度的Nisin(0.1-1000IU/mL)预调节人MSC以确定最佳剂量。用Nisin预处理的MSCs使用显微镜进行表征，流式细胞术,基因表达分析,和功能测定。预处理对生存能力的影响，表型,分化能力，抗菌肽表达，并对MSCs的体外抗菌活性进行了检测。通过在大鼠模型中将来自Nisin预调理与对照MSC的条件培养基局部应用于感染的伤口来评估治疗功效。评估细菌负担，愈合，主机响应,和生存。
■确定了500IU/mL的最佳Nisin剂量，其增加MSC抗菌基因表达和分泌组活性而不损害生存力或干性。Nisin预处理的MSC显示LL37和铁调素的表达上调。与非预处理的MSC相比,来自Nisin预处理的MSC的条件培养基表现出对铜绿假单胞菌生长的约4倍的抑制。在伤口感染模型中,Nisin预处理MSCs的分泌组抑制细菌负荷，加速伤口闭合,调制炎症，与标准MSC治疗相比，存活率提高。
■这项研究探索了用抗菌肽Nisin预处理MSC对增强其抗菌性能同时保持再生能力的作用。来自Nisin预处理的MSC的分泌因子具有减弱感染和促进体内愈合的潜力。该方法为管理抗生素耐药性感染提供了转化的希望，并值得进一步发展。预处理MSC与Nisin可以提供创新，对抗医院病原体和促进组织再生的多方面疗法。
