Abstract
IntroductionThere have been limited advances in the treatment of bone and joint infections, which currently involves a combination of surgery and antibiotic administration. There is a timely need in orthopedics to develop more effective and less invasive forms of antimicrobial prophylaxis and treatment. The antibacterial effect of adult tissue-derived mesenchymal stem cells (MSCs) has recently been investigated against Escherichia coli and Staphylococcus aureus. The main mechanism of action is postulated to be via MSC production of the cationic antimicrobial peptide, LL-37.MethodsThis study examines the antimicrobial activity of adipose-derived human MSCs (ASCs) on S. aureus, specifically examining the role of LL-37 and regulation of its expression. Bacteria colony-forming unit (CFU) assay was used to assess antimicrobial activity.ResultsOur results showed that the ASC-conditioned medium significantly inhibited the growth of S. aureus under standard culture conditions with or without the continued presence of ASCs. Also, the treatment of ASCs with 1,25-dihydroxy vitamin D3 elevated LL-37 expression and enhanced their antimicrobial activity. In support, treatment with the vitamin D receptor inhibitor, GW0742, blocked the antimicrobial activity of ASCs.ConclusionOur findings clearly demonstrate the antimicrobial activity of adult ASCs against S. aureus and implicate a key regulatory role for vitamin D. Further testing in in vivo models is being pursued to assess the potential application of ASCs as a biocompatible, adjunct treatment for musculoskeletal infections.
Highlights
There have been limited advances in the treatment of bone and joint infections, which currently involves a combination of surgery and antibiotic administration
This study examines the antimicrobial activity of adipose-derived human Mesenchymal stem cell (MSC) (ASCs) on S. aureus, examining the role of LL-37 and regulation of its expression
Our findings clearly demonstrate the antimicrobial activity of adult ASCs against S. aureus and implicate a key regulatory role for vitamin D
Summary
There have been limited advances in the treatment of bone and joint infections, which currently involves a combination of surgery and antibiotic administration. There is a timely need in orthopedics to develop more effective and less invasive forms of antimicrobial prophylaxis and treatment. At sites of relatively poor vascularity, can be difficult to treat, often requiring prolonged courses of antimicrobial therapy in association with surgical drainage or debridement [2,3,4]. Antimicrobial activity through systemic and possibly local delivery is often needed to prevent subsequent infections. Recent attempts at local antibiotic delivery through an indwelling catheter in joint infections have only marginally improved outcomes [12,13,14]. Since these methods were introduced in the 1970s, there has been limited advancement in treatment. Our approach is to augment the patient’s own immune system to combat infection
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