Mesenchymal Stem Cell-Derived Exosome Therapy of Microbial Diseases: From Bench to Bed

Abstract

Microbial diseases are a global health threat, leading to tremendous casualties and economic losses. The strategy to treat microbial diseases falls into two broad categories: pathogen-directed therapy (PDT) and host-directed therapy (HDT). As the typical PDT, antibiotics or antiviral drugs directly attack bacteria or viruses through discerning specific molecules. However, drug abuse could result in antimicrobial resistance and increase infectious disease morbidity. Recently, the exosome therapy, as a HDT, has attracted extensive attentions for its potential in limiting infectious complications and targeted drug delivery. Mesenchymal stem cell-derived exosomes (MSC-Exos) are the most broadly investigated. In this review, we mainly focus on the development and recent advances of the application of MSC-Exos on microbial diseases. The review starts with the difficulties and current strategies in antimicrobial treatments, followed by a comprehensive overview of exosomes in aspect of isolation, identification, contents, and applications. Then, the underlying mechanisms of the MSC-Exo therapy in microbial diseases are discussed in depth, mainly including immunomodulation, repression of excessive inflammation, and promotion of tissue regeneration. In addition, we highlight the latest progress in the clinical translation of the MSC-Exo therapy, by summarizing related clinical trials, routes of administration, and exosome modifications. This review will provide fundamental insights and future perspectives on MSC-Exo therapy in microbial diseases from bench to bedside.

Proteomic Profiling of Mesenchymal Stem Cell-Derived Extracellular Vesicles: Impact of Isolation Methods on Protein Cargo

“…Neutrophil degranulation has been identified as one of the main enriched pathways in proteomics analysis of COVID-19 patients (Bankar et al, 2021). EVs derived from MSCs have been demonstrated to possess antimicrobial effects and can effectively enhance the clearance of microbes in an animal model of pneumonia (Xiaolan Wu et al, 2022). However, the specific molecular mechanisms underlying these effects are not yet fully understood.…”

Unveiling the Role of Exosomes in the Pathophysiology of Sepsis: Insights into Organ Dysfunction and Potential Biomarkers

“…It is worth considering that by using MSC-based exosomes, it may be possible to target the infectious agents [139,140]. Exosomes can be modified or engineered to express targeting molecules, such as peptides or antibodies that can recognize and bind to microbial pathogens [141,142]. This targeting can enable the delivery of therapeutic cargo directly to infected cells or pathogens, which can minimize offtarget effects and maximize efficacy [143].…”

The potential use of mesenchymal stem cells-derived exosomes as microRNAs delivery systems in different diseases

“…In viral pneumonia, apart from the suppression of hypercytokinemia, inhibition of viral reproduction and attack on viruses are based pathways of MSC-EXOs treatment. MSC-EXOs miRNAs might bind to the viral genome to inhibit viral RNA transcription or protein translation vital for viral reproduction [133]. Sepsis is an acute deadly factor in COVID-19, and treatment via MSC-EXOs has improved the quantity of recovery in the sepsis animal model.…”