by Germans Trias i Pujol Research Institute

Immune dysregulation and barrier dysfunction in the pathogenesis of inflammatory bowel disease (IBD). The disruption of intestinal homeostasis in IBD is driven by dysbiosis in the gut lumen, loss of the mucus layer, and increased epithelial permeability, allowing bacterial translocation into the lamina propria. Breaches in the epithelial barrier activate dendritic cells, which migrate to mesenteric lymph nodes and promote the differentiation of naïve T cells into pro-inflammatory T helper (Th) cell subsets. Under healthy conditions, regulatory T cells (Tregs) maintain immune homeostasis by secreting anti-inflammatory cytokines such as IL-10 and TGF-β. In IBD, this balance shifts toward pro-inflammatory Th cells, resulting in elevated levels of cytokines including TNF-α, IL-1β, IL-6, IL-17 and IL-23. Additionally, dysregulated innate lymphoid cells (ILCs) exacerbate IBD by producing IL-23, which stimulates IL-17 secretion, further driving inflammation. Credit: Clinical and Translational Medicine (2024). DOI: 10.1002/ctm2.70075

Researchers at Germans Trias i Pujol Research Institute (IGTP) and Institut d’Investigació Sanitària Pere Virgili (IISPV) have conducted a review on the therapeutic potential of extracellular vesicles in inflammatory bowel disease. While this approach remains in the early stages of research, ongoing clinical studies for various diseases already support its viability.

Inflammatory bowel disease is characterized by chronic inflammation of the gastrointestinal tract caused by an imbalance in immune response, encompassing conditions such as Crohn’s disease and ulcerative colitis.

Despite therapeutic advances over the past decade, around half of patients still require surgical interventions within the first ten years after diagnosis. Therefore, researchers and clinicians are dedicated to developing new treatments that effectively modulate immune responses in inflammatory bowel disease.

A collaboration between the Inflammatory Bowel Diseases Research Group (GReMII) at IGTP, the Inflammatory Bowel Disease Research Group (IBODI) at IISPV, the Universitat Rovira i Virgili (URV), and the CIBER of Hepatic and Digestive Diseases (CIBEREHD) has resulted in an extensive review of the potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) as an innovative therapy to treat these conditions. The findings of this work have been published in Clinical and Translational Medicine, a leading journal in translational medicine.

The research is published in the journal Clinical and Translational Medicine.

Dr. Josep Manyé, co-author and researcher at IGTP and CIBEREHD, said, “MSC-EVs represent a promising therapeutic alternative for inflammatory bowel disease, offering significant advantages over conventional cellular therapies. Being an acellular therapy, MSC-EVs carry a lower risk of immunogenicity and tumorigenicity, as well as facilitating storage and handling”.

The review delves into the immunomodulatory, pro-regenerative, anti-apoptotic, and anti-fibrotic properties observed in preclinical studies of MSC-EVs. Dr. Carolina Serena, principal investigator at IISPV and co-author of the study, added, “We have thoroughly analyzed the current understanding of MSC-EVs’ roles in chronic inflammatory processes using advanced transcriptomics, proteomics, and lipidomics techniques, enabling us to pinpoint their mechanisms of action and comprehend how they may restore intestinal homeostasis”.

Additionally, the article explores advancements in the characterization of MSC-EVs, isolation methods, and the challenges to be addressed before translating this innovative therapy to clinical practice. Dr. Laura Clua-Ferré, first author of the publication and researcher at IGTP, emphasized, “The findings of this review provide a robust foundation for further developing innovative therapies for IBD and reflect our teams’ commitment to offering safer and more effective alternatives for patients”.

The research team concludes that MSC-EVs hold the potential to transform therapeutic approaches for inflammatory bowel disease by targeting a novel pathway to treat chronic intestinal inflammation, promote tissue repair, and contribute to the restoration of intestinal balance.

Currently, there are around 20 phase I or II clinical trials investigating these vesicles for different diseases. However, the authors stress the need to overcome certain regulatory and logistical challenges before these therapies can reach patients.

More information: Laura Clua‐Ferré et al, Therapeutic potential of mesenchymal stem cell‐derived extracellular vesicles: A focus on inflammatory bowel disease, Clinical and Translational Medicine (2024). DOI: 10.1002/ctm2.70075

Provided by Germans Trias i Pujol Research Institute

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