未经批准:抗生素耐药性的快速发展需要新的治疗策略来治疗感染。间充质基质细胞(MSC)具有抗菌和免疫调节特性,通过抗菌肽分泌和募集包括中性粒细胞和单核细胞在内的先天免疫细胞介导。人的TLR-3激活,犬和马MSC已被证明在体外增强细菌杀伤和清除,在啮齿动物葡萄球菌生物膜感染模型和自发性多药耐药感染的狗中。这项研究的目的是确定使用抗生素的关节内(IA)TLR-3激活的MSC是否改善了临床参数,并减少了细菌计数和关节液(SF)中的炎性细胞因子浓度。
未经授权:将八匹马接种在一个arsocral关节中,使用耐多药金黄色葡萄球菌(S.金黄色葡萄球菌)。来自三个无关供体的骨髓来源的MSC用TLR-3激动剂多聚肌苷酸激活,聚胞苷酸(pIC)。接受马匹接受MSC加万古霉素(TLR-MSC-VAN),或单独使用万古霉素(VAN),在接种后第1、4、7天和全身庆大霉素。疼痛评分,定量细菌计数(SF,滑膜),SF分析,全血细胞计数,细胞因子浓度(SF,等离子体),影像学改变(MRI,超声,射线照片),评估宏观关节评分和组织学变化.结果报告为平均值±SEM。
未经评估:疼痛评分(d7,P=0.01,15.2±0.2vs.17.9±0.5),超声(d7,P=0.03,9.0±0.6vs.11.8±0.5),定量细菌计数(SFd7,P=0.02,0±0vs.3.4±0.4;滑膜P=0.003,0.4±0.4vs.162.7±18.4),全身中性粒细胞(d4,P=0.03,4.6±0.6vs.7.8±0.6)和血清淀粉样蛋白A(SAA)(d4,P=0.01,1,106.0±659.0vs.2,858.8±141.3;d7,P=0.02,761.8±746.2vs.2,357.3±304.3),和SF乳酸(d7,P<0.0001,5.4±0.2vs.15.0±0.3),SAA(终止,P=0.01,0.0vs.2,094.0±601.6),IL-6(P=0.03,313.0±119.2vs.1,328.2±208.9),和IL-18(P=0.02,11.1±0.5vs.13.3±3.8)在TLR-MSC-VAN与货车马。研究限制包括小马样本量,研究持续时间短,缺乏额外的对照组。
UNASSIGNED:TLR激活的MSC联合抗生素治疗可能是治疗耐药细菌关节感染的一种有希望的方法。
UNASSIGNED: Rapid development of antibiotic resistance necessitates advancement of novel therapeutic strategies to treat infection. Mesenchymal stromal cells (MSC) possess antimicrobial and immunomodulatory properties, mediated through antimicrobial peptide secretion and recruitment of innate immune cells including neutrophils and monocytes. TLR-3 activation of human, canine and equine MSC has been shown to enhance bacterial killing and clearance in vitro, in rodent Staphylococcal biofilm infection models and dogs with spontaneous multi-drug-resistant infections. The objective of this study was to determine if intra-articular (IA) TLR-3-activated MSC with antibiotics improved clinical parameters and reduced bacterial counts and inflammatory cytokine concentrations in synovial fluid (SF) of horses with induced septic arthritis.
UNASSIGNED: Eight horses were inoculated in one tarsocrural joint with multidrug-resistant Staphylococcus aureus (S. aureus). Bone marrow-derived MSC from three unrelated donors were activated with TLR-3 agonist polyinosinic, polycytidylic acid (pIC). Recipient horses received MSC plus vancomycin (TLR-MSC-VAN), or vancomycin (VAN) alone, on days 1, 4, 7 post-inoculation and systemic gentamicin. Pain scores, quantitative bacterial counts (SF, synovium), SF analyses, complete blood counts, cytokine concentrations (SF, plasma), imaging changes (MRI, ultrasound, radiographs), macroscopic joint scores and histologic changes were assessed. Results were reported as mean ± SEM.
UNASSIGNED: Pain scores (d7, P=0.01, 15.2±0.2 vs. 17.9±0.5), ultrasound (d7, P=0.03, 9.0±0.6 vs. 11.8±0.5), quantitative bacterial counts (SF d7, P=0.02, 0±0 vs. 3.4±0.4; synovium P=0.003, 0.4±0.4 vs. 162.7±18.4), systemic neutrophil (d4, P=0.03, 4.6±0.6 vs. 7.8±0.6) and serum amyloid A (SAA) (d4, P=0.01, 1,106.0±659.0 vs. 2,858.8±141.3; d7, P=0.02, 761.8±746.2 vs. 2,357.3±304.3), and SF lactate (d7, P<0.0001, 5.4±0.2 vs. 15.0±0.3), SAA (endterm, P=0.01, 0.0 vs. 2,094.0±601.6), IL-6 (P=0.03, 313.0±119.2 vs. 1,328.2±208.9), and IL-18 (P=0.02, 11.1±0.5 vs. 13.3±3.8) were improved in TLR-MSC-VAN vs. VAN horses. Study limitations include the small horse sample size, short study duration, and lack of additional control groups.
UNASSIGNED: Combined TLR-activated MSC with antibiotic therapy may be a promising approach to manage joint infections with drug resistant bacteria.