Apoptotic vesicles act as natural antibacterial agents for infected wound healing by interfering with the bacterial catabolic process

A large number of apoptotic vesicles (ApoVs) are released during apoptosis, and mesenchymal stem cells (MSCs)-derived ApoVs (MSC-ApoVs) have significant efficacy in the field of tissue regeneration. ApoVs extracted by density gradient centrifugation have a larger volume and wider diameter distribution, high yield and drug loading efficiency, and inherit the apoptotic traces of FasL, phosphatidylserine (PS), ICAM-3, and other parent cells and the ability to target cell membranes. MSC-ApoVs can significantly promote skin wound healing; however, whether they can promote wound healing in the early stages by playing an antibacterial role is unclear. In the present study, human umbilical cord MSC-derived ApoVs (hucMSC-ApoVs) were extracted and prepared. An in vitro antibacterial test confirmed that hucMSC-ApoVs effectively inhibited the growth of bacteria and sterilized bacteria. In vivo experiments revealed that hucMSC-ApoVs can accelerate the healing of infected wounds. Further exploration of the antibacterial mechanism revealed that hucMSC-ApoVs significantly interfered with bacterial catabolic processes. In gram-positive bacteria (MRSA), hucMSC-ApoVs affect the normal metabolic process of bacteria mainly by inhibiting the metabolism of purines, pyrimidines, and other nucleotides of MRSA and arginine biosynthesis, whereas in the gram-negative bacteria E. coli, they affect this process. HucMSC-ApoVs inhibit bacterial metabolic processes such as sulfur, fatty acid, arginine, and proline metabolism; in particular, hucMSC-ApoVs can interfere with the ethanolamine metabolic process in E.coli by regulating a series of ethanolamine genes (Eut) that encode ethanolamine degrading enzymes. These findings suggest that hucMSC-ApoVs are useful natural reagents for inhibiting wound bacterial infection and promoting wound healing.