Hypoxic culture enhances the antimicrobial activity of amnion-derived mesenchymal stem cells, thereby reducing bacterial load and promoting wound healing in diabetic mice.

BACKGROUND: Conditioned medium from amnion-derived mesenchymal stem cells (AMSCs) enhances wound healing, a process that is further improved under hypoxic culture conditions. Diabetic foot ulcers are difficult to treat and are frequently complicated by a high rate of bacterial infections, mainly Staphylococcus aureus, which can lead to limb amputation and death. Here, we topically applied conditioned medium from AMSCs cultured under hypoxic conditions to S. aureus-infected wounds in diabetic mice to investigate its effect on bacterial counts and wound healing. METHODS: We prepared conditioned medium by culturing AMSCs under 21 % or 1 % Oand investigated its effects on S. aureus. We infected skin wounds of diabetic mice with S. aureus and treated these with hydrogels containing the conditioned medium to examine its effect on bacterial inhibition and wound healing. RESULTS: Conditioned medium from AMSCs cultured under 1 % Ocontained higher levels of the antimicrobial peptide LL-37. It significantly inhibited S. aureus growth in vitro, reduced bacterial counts in infected wounds, and facilitated wound closure in diabetic mice. CONCLUSIONS: Hydrogels containing conditioned medium from hypoxically cultured AMSCs inhibited the growth of S. aureus and promoted wound healing in a mouse model of diabetic wounds.