Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province of Sir Run Run Shaw Hospital, MOE Laboratory of Biosystems Homeostasis & Protection of College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Lishui, Zhejiang, 323010, China.
Adv Sci (Weinh). 2024 Nov;11(44):e2401429. doi: 10.1002/advs.202401429. Epub 2024 Oct 8.
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, manifests as chronic intestinal inflammation with debilitating symptoms, posing a significant burden on global healthcare. Moreover, current therapies primarily targeting inflammation can lead to immunosuppression-related complications. Human amniotic epithelial stem cells (hAESCs), which exhibit low immunogenicity and ethical acceptability, have gained attention as potential therapeutics. In this study, it is demonstrated that their encapsulation in a hydrogel and administration via anal injection enhanced the colonic mucosal barrier repair in a murine colitis model induced by dextran sodium sulfate during the recovery phase. The underlying mechanism involved the release of exosomes from hAESCs enriched with microRNA-23a-3p, which post-transcriptionally reduced tumor necrosis factor receptor 1 expression, suppressing the nuclear factor-κB pathway in colonic epithelial cells, thus played a key role in inflammation. The novel approach shows potential for IBD treatment by restoring intestinal epithelial homeostasis without the immunosuppressive therapy-associated risks. Furthermore, the approach provides an alternative strategy to target the key molecular pathways involved in inflammation and promotes intestinal barrier function using hAESCs and their secreted exosomes. Overall, this study provides key insights to effectively treat IBD, addresses the unmet needs of patients, and reduces related healthcare burden.
炎症性肠病（IBD），包括溃疡性结肠炎和克罗恩病，表现为慢性肠道炎症，伴有使人虚弱的症状，给全球医疗保健带来了重大负担。此外，目前主要针对炎症的治疗方法可能会导致与免疫抑制相关的并发症。人羊膜上皮干细胞（hAESCs）具有较低的免疫原性和伦理可接受性，已成为潜在治疗方法的关注点。在这项研究中，证明了在恢复阶段通过葡聚糖硫酸钠诱导的小鼠结肠炎模型中，通过肛门注射将其包封在水凝胶中可以增强结肠黏膜屏障的修复。潜在的机制涉及富含 microRNA-23a-3p 的 hAESCs 释放外泌体，该外泌体在后转录水平降低肿瘤坏死因子受体 1 的表达，从而抑制结肠上皮细胞中的核因子-κB 途径，从而在炎症中发挥关键作用。这种新方法通过恢复肠道上皮细胞的稳态而没有免疫抑制治疗相关的风险，显示出治疗 IBD 的潜力。此外，该方法为使用 hAESCs 和它们分泌的外泌体靶向炎症的关键分子途径并促进肠道屏障功能提供了一种替代策略。总体而言，这项研究为有效治疗 IBD 提供了关键的见解，满足了患者的未满足需求，并减轻了相关的医疗保健负担。
