Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration

Abstract

Inflammatory bowel disease (IBD) remains a severe disease for most patients, with its incidence and prevalence increasingly globally. Currently, there is no effective treatments for IBD, and traditional treatments have multiple side effects. Therefore, novel therapeutic strategies or alternative drugs are urgently needed. Previous studies have shown that mesenchymal stem cell-derived exosomes have exhibited promising therapeutic effects on inflammatory disease. Here, we performed intravenous injection of human adipose mesenchymal stem cell (hADSC)-derived exosomes (hADSC-Exo) in a DSS-induced IBD mouse model and found that hADSC-Exo promoted functional recovery, downregulated inflammatory responses, reduced intestine cell apoptosis, increased epithelial regeneration and maintained intestinal barrier integrity. Moreover, we established a colon organoid, hADSC-Exo and TNF-α co-cultured system to explore the protective effect of hADSC-Exo on integrity of intestine mucosa and epithelial regeneration. We showed that hADSC-Exo not only can promote the proliferation and regeneration of Lgr5 + ISCs and epithelial cells but also ameliorate the inflammation damage in TNF-α induced inflammatory damaged mice colon organoids. Taken together, our findings indicate that hADSC-Exo protects intestine integrity, activates intestine epithelial cell and ISCs proliferation, suggesting that hADSC-Exo might be a potential effective treatment approach for IBD. We also provide a theoretical basis for new therapeutic strategies for cell-free therapy in inflammatory bowel disease.

Exosomes as Promising Nanostructures in Diabetes Mellitus: From Insulin Sensitivity to Ameliorating Diabetic Complications

“…68 In inflammatory bowel disease, exosomes can improve epithelial regeneration and induce repair of the intestinal barrier with TSG-6 overexpression. 69,70 Based on these studies, exosomes function as therapeutic agents in various diseases, and this review focuses on DM therapy.…”

Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Promote Peritoneal Healing by Activating MAPK-ERK1/2 and PI3K-Akt to Alleviate Postoperative Abdominal Adhesion

“…In general, intravenous injection of EVs is the most common method of EVs delivery [ 55 – 57 ]. For example, the delivery of EVs prepared from mice human umbilical cord MSC-EVs (HUC-MSC-EVs) carrying miRNA-326 inhibits neddylation to relieve inflammatory bowel disease (IBD) [ 56 ].…”

Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents

“…Notably, the anti-inflammatory behavior of ASC-derived EVs could also be exploited in inflammatory bowel disease (IBD), for which there is no effective and safe treatment. Yu and colleagues [78] recently reported in a mouse model of IBD that exosomes from human ASCs protected the integrity of the gut by activating the proliferation of intestinal epithelial and stem cells. Moreover, the anti-inflammatory/immunomodulatory potential of ASC-derived EVs is now being actively investigated for possible applications in acute and chronic inflammatory conditions, including experimental allergic airway models, ultraviolet B ray exposure-induced skin alteration or inflammation associated with traumatic brain injury [79][80][81].…”