Extracellular Vesicles: Novel Potential Therapeutic Agents in Inflammatory Bowel Diseases

Abstract

Patients affected by inflammatory bowel diseases (IBD) can nowadays benefit from a growing number of pharmacological options. However, in moderate-to-severe cases, the therapeutic response is still far from optimal, and treatment changes and optimizations are often required. Thus, researchers in this field are strongly engaged in studies aiming to identify new potential therapeutic targets. Extracellular vesicles (EVs) are tiny subcellular bodies with a phospholipid bilayer envelope containing bioactive molecules, which are released from different cells and are involved in intercellular communication. Recent pre-clinical data show their emerging role in the pathogenesis and treatment of IBD. In our review, we summarize current evidence about the function of EVs as active therapeutic agents in ulcerative colitis and Crohn's disease, analyzing the properties of EVs derived from different cellular sources and the mechanisms through which they may improve intestinal inflammation.

Keywords: extracellular vesicles; inflammatory bowel diseases; novel therapeutic agents.

Figure 1

Structure and functions of EVs in GI tract. EVs encompass apoptotic bodies, microvesicles, and exosomes, differentiated based on their size. EVs are extracellular bodies with a phospholipid membrane containing heterogeneous molecules, such as proteins, lipids, and genetic material. They interact with target cells through either internalization and subsequent release of the internal content or adhesion to specific receptors and subsequent activation of intracellular pathways. In IBD pre-clinical models, EVs deriving from epithelial cells, mesenchymal stem cells, gut microbiota, and some ingesta proved to have a beneficial role on GI inflammation through different mechanisms, notably modulating pro/anti-inflammatory status, promoting intestinal re-epithelization and strengthening gut barrier.