Combinational therapy of mesenchymal stromal cells and Ophiophagus hannah L-amino acid oxidase in the treatment of infected cutaneous wounds

Abstract

Mesenchymal stromal cells (MSCs) and Ophiophagus hannah L-amino acid oxidase (Oh-LAAO) have been reported to exhibit antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). Published data have indicated that synergistic antibacterial effects could be achieved by co-administration of two or more antimicrobial agents. However, this hypothesis has not been proven in a cell and protein based combination. In this study, we investigate if co-administration of MSCs and Oh-LAAO into a mouse model of MRSA infected wounds would be able to result in a synergistic antibacterial effect. MSCs and Oh-LAAO were isolated and characterized by standard methodologies. The effect of the co-administration was evaluated with a C57/BL6 mouse model of MRSA infected full-thickness wound. Individual treatments with MSCs and Oh-LAAO in the infected model resulted in reduction of MRSA load by one order in magnitude compared to untreated controls. Similar wound healing and improvements in histological parameters were observed between the two groups. Co-administration of MSCs and Oh-LAAO reduced bacterial burden by two orders in magnitude. Wound closure measurements and histology analysis of biopsies obtained from the combinational therapy group indicated significant enhancement in the wound healing process compared to all other groups. We demonstrated that co-administration of MSCs and Oh-LAAO into a mouse model of MRSA infected wounds exhibited a synergistic antibacterial effect which significantly reduced the bacterial count and accelerate the wound healing process.