Combinational therapy with antibiotics and antibiotic-loaded adipose-derived stem cells reduce abscess formation in implant-related infection in rats

抗生素和载抗生素的脂肪干细胞联合治疗可减少大鼠植入物相关感染的脓肿形成

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作者:Junya Yoshitani, Tamon Kabata, Hiroshi Arakawa, Yukio Kato, Takayuki Nojima, Katsuhiro Hayashi, Masaharu Tokoro, Naotoshi Sugimoto, Yoshitomo Kajino, Daisuke Inoue, Ken Ueoka, Yuki Yamamuro, Hiroyuki Tsuchiya

Abstract

Implant-related infection is difficult to treat without extended antibiotic courses. However, the long-term use of antibiotics has led to the development of multidrug- and methicillin-resistant Staphylococcus aureus. Thus, alternatives to conventional antibiotic therapy are needed. Recently, mesenchymal stem cells have been shown to have antimicrobial properties. This study aimed to evaluate the antimicrobial activity and therapeutic effect of local treatment with antibiotic-loaded adipose-derived stem cells (ADSCs) plus an antibiotic in a rat implant-associated infection model. Liquid chromatography/tandem mass spectrometry revealed that ADSCs cultured in the presence of ciprofloxacin for 24 h showed time-dependent antibiotic loading. Next, we studied the therapeutic effects of ADSCs and ciprofloxacin alone or in combination in an implant-related infection rat model. The therapeutic effects of ADSCs plus antibiotics, antibiotics, and ADSCs were compared with no treatment as a control. Rats treated with ADSCs plus ciprofloxacin had the lowest modified osteomyelitis scores, abscess formation, and bacterial burden on the implant among all groups (P < 0.05). Thus, local treatment with ADSCs plus an antibiotic has an antimicrobial effect in implant-related infection and decrease abscess formation. Thus, our findings indicate that local administration of ADSCs with antibiotics represents a novel treatment strategy for implant-associated osteomyelitis.

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