Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Adv Sci (Weinh). 2023 Nov;10(32):e2303349. doi: 10.1002/advs.202303349. Epub 2023 Sep 27.
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 (MSC EVs) is developed to treat IBD. The MSC EVs prepared through lentivirus-mediated gene transfection technology show ideal anti-inflammatory and damage repair function. By encapsulating MSC EVs into dopamine methacrylamide-modified hydrogel, a bioadhesive EVs microcarrier via microfluidic technology is fabricated. The resultant microcarriers exhibit ideal MSC EVs sustained release effect and effective wet adhesion property. Furthermore, the therapeutic potential of MSC 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 MSC EVs-loaded microcarriers provide a promising strategy for the biomedical application of MSC-derived EVs, and broaden the clinical potential of MSC therapy.
间充质干细胞(MSC)治疗是炎症性肠病(IBD)治疗的一种有前途的候选方法,而克服幼稚播种细胞功能的局限性并实现有效的肠道靶向仍然是一个挑战。在这里,开发了一种携带白细胞介素 27(IL-27)MSC 衍生细胞外囊泡(MSC EVs)的生物黏附微球来治疗 IBD。通过慢病毒介导的基因转染技术制备的 MSC EVs 表现出理想的抗炎和损伤修复功能。通过将 MSC EVs 包封到多巴胺甲基丙烯酰胺修饰的水凝胶中,通过微流控技术制备了生物黏附 EVs 微载体。所得微载体表现出理想的 MSC EVs 持续释放效果和有效的湿黏附性能。此外,还证明了负载 MSC EVs 的微载体在治疗 IBD 中的治疗潜力。通过对 IBD 大鼠进行直肠给药,发现微载体可以牢固地锚定在结肠表面,减轻炎症反应并修复受损的屏障。因此,生物黏附 MSC EVs 负载的微载体为 MSC 衍生 EVs 的生物医学应用提供了一种有前途的策略,并拓宽了 MSC 治疗的临床潜力。