Exosome‐mediated effects and applications in inflammatory bowel disease

Abstract

Gut mucosal barriers, including chemical and physical barriers, spatially separate the gut microbiota from the host immune system to prevent unwanted immune responses that could lead to intestinal inflammation. In inflammatory bowel disease (IBD), there is mucosal barrier dysfunction coupled with immune dysregulation and dysbiosis. The discovery of exosomes as regulators of vital functions in both physiological and pathological processes has generated much research interest. Interestingly, exosomes not only serve as natural nanocarriers for the delivery of functional RNAs, proteins, and synthetic drugs or molecules, but also show potential for clinical applications in tissue repair and regeneration as well as disease diagnosis and prognosis. Biological or chemical modification of exosomes can broaden, change and enhance their therapeutic capability. We review the modulatory effects of exosomal proteins, RNAs and lipids on IBD components such as immune cells, the gut microbiota and the intestinal mucosal barrier. Mechanisms involved in regulating these factors towards attenuating IBD have been explored in several studies employing exosomes derived from different sources. We discuss the potential utility of exosomes as diagnostic markers and drug delivery systems, as well as the application of modified exosomes in IBD.

Exosomes in Intestinal Inflammation

“…Many studies have used exosomes from a variety of starting materials to study the process of IBD alleviation and related factors of interest. Translational studies are being conducted to tap into the possible use of exosomes as diagnostic markers and drug delivery systems, and also on the utility of modified exosomes in IBD therapy ( Ocansey et al, 2020 ). Many of the studies cited in this review do not differentiate between the different types of EVs like exosomes, endosomes and MVBs, hence for the sake of convenience we have used the general term EVs while describing study findings.…”

Cellular and molecular mediators of lymphangiogenesis in inflammatory bowel disease

“…The VEGF-C-dependent lymphangiogenesis occurs via miR-132 directly targeting Smad-7 and modulating transforming growth factor (TGF)-β/Smad signaling [ 129 ]. As potent regulators of inflammatory-associated lymphangiogenesis, various sources of stem cells and their secretory products are being explored as a possible treatment option for IBD [ 130 , 131 ]. The various pathways linked with lymphangiogenesis are summarized in Table 1 .…”

Regulatory Effect of Mesenchymal Stem Cells on T Cell Phenotypes in Autoimmune Diseases

“…However, it is important to note that regardless of the success witnessed in MSC therapy in IBD, it is still confronted with several challenges such as severe adverse events, encouraging tumor growth and metastasis, among other reactions as detailed in recent reviews by Ocansey et al [ 52 , 53 ]. There is the need to identify supportive or combined therapies of MSC transplantation and also choose the most appropriate stem cell and treatment approach to enhance effectiveness while avoiding the occurrence of serious adverse events [ 54 ].…”

“…In a meta-analysis study that evaluated the efficacy and safety of MSC treatment in SLE patients, the researchers report that the MSC group showed significantly decreased SLE disease activity index, as well as decreased urine protein, and increased complement C3 [ 73 ]. A meta-analysis of the animal model of lupus nephritis also confirmed that MSC treatment resulted in lower levels of disease-associated elements such as double-stranded DNA (ds-DNA), antinuclear antibody (ANA), serum creatinine (Scr), blood urea nitrogen (BUN), proteinuria, and renal sclerosis score, as well as higher albumin levels [ 53 ]. Several other studies have reported the promising effect of MSCs in SLE experimental studies and clinical trials [ 74 ].…”