Bioadhesive Microcarriers Encapsulated with IL‐27 High Expressive MSC Extracellular Vesicles for Inflammatory Bowel Disease Treatment

Abstract

Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient intestinal targeting remains a challenge. Here, a bioadhesive microparticle carrying interleukin‐27 (IL‐27) MSC‐derived extracellular vesicles (MSCIL‐27 EVs) is developed to treat IBD. The MSCIL‐27 EVs prepared through lentivirus‐mediated gene transfection technology show ideal anti‐inflammatory and damage repair function. By encapsulating MSCIL‐27 EVs into dopamine methacrylamide‐modified hydrogel, a bioadhesive EVs microcarrier via microfluidic technology is fabricated. The resultant microcarriers exhibit ideal MSCIL‐27 EVs sustained release effect and effective wet adhesion property. Furthermore, the therapeutic potential of MSCIL‐27 EVs‐loaded microcarriers in treating IBD is demonstrated. Through giving IBD rats a rectal administration, it is found that the microcarriers can firmly anchor to the surface of colon, reduce the inflammatory response, and repair the damaged barrier. Therefore, the bioadhesive MSCIL‐27 EVs‐loaded microcarriers provide a promising strategy for the biomedical application of MSC‐derived EVs, and broaden the clinical potential of MSC therapy.

Recent advances in extracellular vesicles for therapeutic cargo delivery

“…Nie et al transfected mesenchymal stem cells (MSCs) with lentivirus to overexpress IL-27 and thereby generated IL-27-loaded exosomes. In this study, IL-27-loaded exosomes inhibited inflammatory responses and rescued intestinal barrier dysfunction 44 . Jung et al generated hepatic TM4SF5-overexpressing (Alb-Tm4sf5 TG) mice and isolated TM4SF5-loaded exosomes from liver-circulating fluids.…”