Broad-Spectrum Antibacterial Effects of Human Adipose-Derived Stromal Cells

Abstract

Introduction Many pathological conditions may benefit from cell therapy using mesenchymal stromal cells, particularly from adipose tissue (ASCs). Cells may be grafted in an environment with a remnant polymicrobial component. The aim is to investigate the behavior of ASCs when brought in contact with a large panel of bacteria. Materials and Methods Carboxyfluorescein-labelled bacterial interaction with ASCs was followed by confocal time-lapse microscopy. Costaining with LAMP-1 was also analyzed. Viability of 4 gram-negative and 4 gram-positive bacterial strains after 6 h of coculture with ASCs was assessed by agar colony counting and by flow cytometry using SYTO-62®/propidium iodide (PI) for membrane permeabilization and DiOC6 for depolarization. A murine model of periodontitis was used to assess in vivo antibacterial capacities of ASCs. Results A significant increase of PI-positive events for all bacterial strains and an increase of the DiOC6 signal were obtained after contact with ASCs. The number of CFU was also significantly decreased for several bacterial strains. 0.4 μm transwell systems illustrated the necessary direct contact to induce maximal bacterial membrane damages. Some bacteria were observed into phagolysosomes, confirming macrophage-like properties of ASCs. In vivo, the bacterial load was significantly lower in the ASC-grafted side compared to the control. Conclusion Our results highlight for the first time a broad range of antibacterial actions of ASCs, by phagocytosis, secretion of oxygenated free radicals and antibacterial molecules. These data are in line with the development of new therapeutic strategies based on ASC transplantation, appropriated in immune-dysbiotic tissue context such as periodontitis or chronic wounds.

MSCs and Inflammatory Cells Crosstalk in Regenerative Medicine: Concerted Actions for Optimized Resolution Driven by Energy Metabolism

“…Monsarrat et al showed that ASCs could disturb bacterial division, induce bacterial membrane permeabilization through ROS secretion and phagocyte Gram-positive and Gram-negative bacteria. Moreover, in a mouse model of pathogen-induced periodontitis, engraftment of human ASCs decreases the bacterial load (111). Unstimulated conditioned medium of human BM-MSCs shows an antimicrobial activity as well as an inhibitory effect on biofilm formation of V. cholerea (112).…”

Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

“…It is suggested that Wharton Jelly Umbilical matrix (WJ-MSCs) [103] may be preferable in sepsis modeling [104]. In vitro phenomena such as phagocytosis, secretion of oxygen free radicals, and antibacterial molecules were reported for ASCs when placed in contact with a large panel of both Gram-negative and Gram-positive bacteria, whereas in vivo they reduced the bacterial load of murine periopathogens [105]. The amniotic membrane homogenate has antibacterial properties, and the amniotic membrane has the potential to be used against multidrug-resistant bacteria [106].…”

Dodging COVID-19 infection: low expression and localization of ACE2 and TMPRSS2 in multiple donor-derived lines of human umbilical cord-derived mesenchymal stem cells

“…Mesenchymal stem cells (MSCs) [ 12 , 13 ] exert anti-inflammatory [ 14 – 16 ], anti-bacterial, anti-protozoan and anti-viral [ 17 – 20 ] effects making them a possible treatment for COVID-19-related complications [ 21 – 24 ]. MSCs produce several types of cytokines via paracrine secretion or have direct interactions with immune cells, resulting in immunomodulation [ 25 ].…”