Enayati Sara, Halabian Raheleh, Saffarian Parvaneh, Aghamollaei Hossein, Saeedi Pardis
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences Tehran, Iran.
Regen Ther. 2024 Jun 5;26:161-169. doi: 10.1016/j.reth.2024.05.015. eCollection 2024 Jun.
Nosocomial infections caused by multidrug-resistant are a considerable public health threat, requiring innovative therapeutic approaches.
This study explored preconditioning mesenchymal stem cells (MSCs) with the antimicrobial peptide Nisin to enhance their antibacterial properties while maintaining regenerative capacity.
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 were tested . 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.
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 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.
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 . 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.
多重耐药菌引起的医院感染是对公共卫生的重大威胁，需要创新的治疗方法。
本研究探索用抗菌肽乳链菌肽预处理间充质干细胞（MSC），以增强其抗菌特性，同时保持再生能力。
用不同浓度的乳链菌肽（0.1 - 1000 IU/mL）预处理人MSC，以确定最佳剂量。通过显微镜检查、流式细胞术、基因表达分析和功能测定对经乳链菌肽预处理的MSC进行表征。测试预处理对MSC的活力、表型、分化能力、抗菌肽表达以及对[具体细菌名称未给出]的抗菌活性的影响。通过将经乳链菌肽预处理的MSC与对照MSC的条件培养基局部应用于大鼠模型中的感染伤口，评估细菌负荷、愈合情况、宿主反应和存活率，来评价治疗效果。
确定了500 IU/mL的最佳乳链菌肽剂量，该剂量可增加MSC抗菌基因表达和分泌组活性，而不影响其活力或干性。经乳链菌肽预处理的MSC显示LL37和铁调素的表达上调。与未预处理的MSC相比，经乳链菌肽预处理的MSC的条件培养基对[具体细菌名称未给出]生长的抑制作用高出约4倍。在伤口感染模型中，与标准MSC治疗相比，经乳链菌肽预处理的MSC的分泌组可抑制细菌载量、加速伤口闭合、调节炎症并提高存活率。
本研究探索了用抗菌肽乳链菌肽预处理MSC对增强其抗菌特性同时保持再生能力的影响。经乳链菌肽预处理的MSC分泌的因子有可能减轻感染并促进愈合。该方法在管理耐药性感染方面具有转化前景，值得进一步开发。用乳链菌肽预处理的MSC可能为对抗医院病原体和促进组织再生提供创新的多方面治疗方法。
