Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.
Department of Pathology and Laboratory Medicine, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.
Sci Rep. 2023 Mar 9;13(1):3949. doi: 10.1038/s41598-023-30087-z.
Periprosthetic joint infection (PJI) is characterized by biofilm infection, which is difficult to alleviate while preserving implant integrity. Furthermore, long-term antibiotic therapy may increase the prevalence of drug-resistant bacterial strains, necessitating a non-antibacterial approach. Adipose-derived stem cells (ADSCs) exert antibacterial effects; however, their efficacy in PJI remains unclear. This study investigates the efficacy of combined intravenous ADSCs and antibiotic therapy in comparison to antibiotic monotherapy in a methicillin-sensitive Staphylococcus aureus (MSSA)-infected PJI rat model. The rats were randomly assigned and equally divided into 3 groups: no-treatment group, antibiotic group, ADSCs with antibiotic group. The ADSCs with antibiotic group exhibited the fastest recovery from weight loss, with lower bacterial counts (p = 0.013 vs. no-treatment group; p = 0.024 vs. antibiotic group) and less bone density loss around the implants (p = 0.015 vs. no-treatment group; p = 0.025 vs. antibiotic group). The modified Rissing score was used to evaluate localized infection on postoperative day 14 and was the lowest in the ADSCs with antibiotic group; however, no significant difference was observed between the antibiotic group and ADSCs with antibiotic group (p < 0.001 vs. no-treatment group; p = 0.359 vs. antibiotic group). Histological analysis revealed a clear, thin, and continuous bony envelope, a homogeneous bone marrow, and a defined, normal interface in the ADSCs with antibiotic group. Moreover, the expression of cathelicidin expression was significantly higher (p = 0.002 vs. no-treatment group; p = 0.049 vs. antibiotic group), whereas that of tumor necrosis factor (TNF)-α and interleukin(IL)-6 was lower in the ADSCs with antibiotic group than in the no-treatment group (TNF-α, p = 0.010 vs. no-treatment group; IL-6, p = 0.010 vs. no-treatment group). Thus, the combined intravenous ADSCs and antibiotic therapy induced a stronger antibacterial effect than antibiotic monotherapy in a MSSA-infected PJI rat model. This strong antibacterial effect may be related to the increased cathelicidin expression and decreased inflammatory cytokine expression at the site of infection.
假体周围关节感染（PJI）的特征为生物膜感染，在保留植入物完整性的同时，这种感染难以缓解。此外，长期的抗生素治疗可能会增加耐药菌的流行，因此需要一种非抗菌方法。脂肪来源的干细胞（ADSCs）具有抗菌作用，但它们在 PJI 中的疗效尚不清楚。本研究旨在比较静脉注射 ADSCs 联合抗生素治疗与单纯抗生素治疗在耐甲氧西林金黄色葡萄球菌（MSSA）感染的 PJI 大鼠模型中的疗效。将大鼠随机分为 3 组：未治疗组、抗生素组、ADSCs 联合抗生素组。ADSCs 联合抗生素组从体重减轻中恢复得最快，细菌计数较低（p = 0.013 比未治疗组；p = 0.024 比抗生素组），植入物周围的骨密度损失较少（p = 0.015 比未治疗组；p = 0.025 比抗生素组）。改良 Rissing 评分用于评估术后第 14 天的局部感染，ADSCs 联合抗生素组的评分最低；然而，抗生素组和 ADSCs 联合抗生素组之间无显著差异（p < 0.001 比未治疗组；p = 0.359 比抗生素组）。组织学分析显示，ADSCs 联合抗生素组的骨皮质清晰、薄且连续，骨髓均匀，界面正常。此外，ADSCs 联合抗生素组的抗菌肽表达明显升高（p = 0.002 比未治疗组；p = 0.049 比抗生素组），而肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6 的表达低于未治疗组（TNF-α，p = 0.010 比未治疗组；IL-6，p = 0.010 比未治疗组）。因此，与单纯抗生素治疗相比，静脉注射 ADSCs 联合抗生素治疗在 MSSA 感染的 PJI 大鼠模型中诱导了更强的抗菌作用。这种强大的抗菌作用可能与感染部位抗菌肽表达增加和炎症细胞因子表达减少有关。
