Therapeutic potential of mesenchymal stem cell‐derived extracellular vesicles: A focus on inflammatory bowel disease

Abstract Background Mesenchymal stem cell‐derived extracellular vesicles (MSC‐EVs) have emerged as key regulators of intercellular communication, orchestrating essential biological processes by delivering bioactive cargoes to target cells. Available evidence suggests that MSC‐EVs can mimic the functions of their parental cells, exhibiting immunomodulatory, pro‐regenerative, anti‐apoptotic, and antifibrotic properties. Consequently, MSC‐EVs represent a cell‐free therapeutic option for patients with inflammatory bowel disease (IBD), overcoming the limitations associated with cell replacement therapy, including their non‐immunogenic nature, lower risk of tumourigenicity, cargo specificity and ease of manipulation and storage. Main Topics Covered This review aims to provide a comprehensive examination of the therapeutic efficacy of MSC‐EVs in IBD, with a focus on their mechanisms of action and potential impact on treatment outcomes. We examine the advantages of MSC‐EVs over traditional therapies, discuss methods for their isolation and characterisation, and present mechanistic insights into their therapeutic effects through transcriptomic, proteomic and lipidomic analyses of MSC‐EV cargoes. We also discuss available preclinical studies demonstrating that MSC‐EVs reduce inflammation, promote tissue repair and restore intestinal homeostasis in IBD models, and compare these findings with those of clinical trials. Conclusions Finally, we highlight the potential of MSC‐EVs as a novel therapy for IBD and identify challenges and opportunities associated with their translation into clinical practice. Highlights The source of mesenchymal stem cells (MSCs) strongly influences the composition and function of MSC‐derived extracellular vesicles (EVs), affecting their therapeutic potential. Adipose‐derived MSC‐EVs, known for their immunoregulatory properties and ease of isolation, show promise as a treatment for inflammatory bowel disease (IBD). MicroRNAs are consistently present in MSC‐EVs across cell types and are involved in pathways that are dysregulated in IBD, making them potential therapeutic agents. For example, miR‐let‐7a is associated with inhibition of apoptosis, miR‐100 supports cell survival, miR‐125b helps suppress pro‐inflammatory cytokines and miR‐20 promotes anti‐inflammatory M2 macrophage polarisation. Preclinical studies in IBD models have shown that MSC‐EVs reduce intestinal inflammation by suppressing pro‐inflammatory mediators (e.g., TNF‐α, IL‐1β, IL‐6) and increasing anti‐inflammatory factors (e.g., IL‐4, IL‐10). They also promote mucosal healing and strengthen the integrity of the gut barrier, suggesting their potential to address IBD pathology.