Application of Exosomes-Derived Mesenchymal Stem Cells in Treatment of Fungal Diseases: From Basic to Clinical Sciences

Abstract

Fungal diseases such as candidiasis are some of the deadliest diseases among immunocompromised patients. These fungi naturally exist on human skin and throughout the digestive system. When the microbiota balance becomes upset, these fungi become pathogenic and potentially lethal. At the pathogenesis of fungal diseases, host immune system response is diverse. At the early stages of fungal pathogenesis such as Candida albicans, it was shown that these fungi use the immune cells of the host body and cause malfunction the early induction of proinflammatory cytokines of the host body leading to a reduction in their numbers. However, at some stages of fungal diseases, the immune response is severe. Despite many treatments already being available, it seems that one of the best treatments could be an immune-stimulatory agent. Some of the subsets of MSCs and exosome-derived cells, as a cell-to-cell communicator agent, have many roles in the human body, including anti-inflammatory and immune-modulatory effects. However, the TLR4-primed and IL-17+ subsets of MSCs have been shown to have immune-stimulatory effects. These subsets of the MSCs produce pro-inflammatory cytokines and reduce immunosuppressive cytokines and chemokines. Thus, they could trigger inflammation and stop fungal pathogenesis. As some biological activities and molecules inherit elements of their exosomes from their maternal cells, the exosome-derived TLR4-primed and IL-17+ subsets of MSCs could be a good candidate for fighting against fungal diseases. The applications of exosomes in human diseases are well-known and expanding. It is time to investigate the exosomes application in fungal diseases. In this review, the probable role of exosomes in treating fungal diseases is explored.

Macrophage-derived CD36 + exosome subpopulations as novel biomarkers of Candida albicans infection

“…Recent studies increasingly underscore the significance of exosomes in both biophysiological and pathological processes, highlighting their evolving roles in diagnostics and therapeutics across a spectrum of diseases 20 – 23 . Furthermore, the exosomes secreted by host cells in response to fungal infections have garnered considerable attention in the scientific community, becoming a focal point of extensive research 24 , 25 . This growing body of evidence reflects the expanding understanding of exosomal functions and their potential implications in disease management and treatment strategies.…”

Non-Clinical Safety Evaluation of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Cynomolgus Monkeys

“…First of all, exosomes have complex biological characteristics and functions, and their pharmacokinetics, action pathway, target and action mechanism in vivo are still unknown. 5 The researchers also pointed out that several key problems need to be solved in the successful transformation of exosomes into clinical use, such as production methods, quantification and characterization, pharmacokinetics and targeting, and safety evaluation. 6 Some researchers also said that it is very important to make a comprehensive analysis of exosomes (including protein, lipids and nucleic acids) and carry out animal toxicology research to predict any unforeseen safety problems.…”