Abstract
BACKGROUND: New therapeutic strategies are needed to treat tuberculosis (TB). The antimicrobial peptide PK34 has a good ability to clear Mycobacterium tuberculosis (Mtb) and is not prone to drug resistance and adverse reactions. Mesenchymal stem cells (MSCs) can also be used as an adjunctive therapy for the treatment of TB. However, there have been no studies combining the two for the treatment of Mtb infection. METHODS: We aimed to construct bone-derived mesenchymal stem cells secreting the antimicrobial peptide PK34 (named Plent-PK34-BMSCs) and to investigate their roles in both in vitro and in vivo Mtb H37Rv infection models. RESULTS: We successfully constructed Plent-PK34-BMSCs that secrete and express the antimicrobial peptide PK34, and demonstrated that PK34 modified MSCs significantly enhanced their in vitro and in vivo antibacterial ability and cytoprotective effects. The cytokine results showed that Plent-PK34-BMSCs increased the levels of anti-inflammatory factors IL-4 and IL-10 in the cell supernatant, decreased the levels of pro-inflammatory factors IL-6 in the serum of the mice. In addition, lung tissue analysis results showed that mice treated with Plent-PK34-BMSCs had reduced infiltration and congestion of inflammatory cells in lung tissue, significantly reduced lung injury, and exhibited better preservation of lung structure. CONCLUSIONS: PK34 modification enhanced the therapeutic efficacy of MSCs in Mtb infection models, and Plent-PK34-BMSCs transplantation has the potential to treat TB.