Abstract
Abstract Background Crohn’s disease (CD) is a chronic, idiopathic inflammatory bowel disease characterised by discontinuous lesions and transmural inflammation that can affect the entire gastrointestinal tract. Despite recent therapeutic advancements, around 50% of patients with CD require at least one surgical intervention within ten years of diagnosis, with 80% of these patients developing new lesions following surgery.1 Emerging evidence highlights that the therapeutic efficacy of mesenchymal stem cells (MSCs) is predominantly attributed to the extracellular vesicles (EVs) they secrete.2 These nanovesicles have gained recognition as critical mediators of anti-inflammatory responses and tissue repair. This research seeks to develop MSC-derived EV-based acellular therapy to regulate the immune response, heal the intestinal mucosa, restore gut microbiota balance, and ultimately reduce disease severity and recurrence. Methods Inclusion criteria for selecting healthy donors for obtaining EVs derived from subcutaneous adipose tissue MSCs include sex, age <40 years, and BMI <25 kg/m². Exclusion criteria include smokers, alcohol consumers, and patients with cancer or other chronic conditions. EV isolation was performed using size-exclusion chromatography, and characterisation was conducted via flow cytometry and electron microscopy (Cryo-TEM). To assess the therapeutic properties of the EVs, biopsies of inflamed perilesional adipose tissue and intestinal mucosa from CD patients were treated with a dose of 150 µg/mL for 20 hours. Finally, the gene expression profile of pro-inflammatory markers (TNFα, IL1B, IL6, and CCL2) and anti-inflammatory markers (IL10) was analysed by qPCR. Results The isolation and characterization of EVs were successfully demonstrated, along with their functional efficacy in both adipose and intestinal explant models. Explants treatment with EVs resulted in a significant reduction in pro-inflammatory cytokines, with IL-1β and TNF-α expression decreased by up to 200-fold compared to untreated explants, while also promoting a notable increase in the anti-inflammatory marker IL-10. Conclusion Adipose tissue-derived EVs could regulate inflammation and promote the regeneration of the intestinal barrier, thus reducing the severity of CD and lowering the risk of post-surgical recurrence. References 1Golovics PA, Mandel MD, Lovasz BD, Lakatos PL. Inflammatory bowel disease course in Crohn’s disease: Is the natural history changing? World J Gastroenterol. 2014;20(12):3198-3207. 2.Zhou Y, Yamamoto Y, Xiao Z, Ochiya T. The immunomodulatory functions of mesenchymal stromal/stem cells mediated via paracrine activity. J Clin Med. 2019;8(1)
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call