Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
J Tissue Eng Regen Med. 2018 Apr;12(4):923-935. doi: 10.1002/term.2506. Epub 2017 Oct 19.
Disruption of normal barrier function is a fundamental factor in the pathogenesis of inflammatory bowel disease, which includes increased epithelial cell death, modified mucus configuration, altered expression and distribution of tight junction proteins, along with a decreased expression of antimicrobial peptides. Inflammatory bowel disease is associated with life-long morbidity for affected patients, and both the incidence and prevalence is increasing globally, resulting in substantial economic strain for society. Mucosal healing and re-establishment of barrier integrity are associated with clinical remission, as well as with an improved patient outcome. Hence, these factors are vital treatment goals, which conventionally are achieved by a range of medical treatments, although none are effective in all patients, resulting in several patients still requiring surgery at some point. Therefore, novel treatment strategies to accomplish mucosal healing and to re-establish normal barrier integrity in inflammatory bowel disease are warranted, and luminal stem cell-based approaches might have an intriguing potential. Transplantation of in vitro expanded intestinal epithelial stem cells derived either directly from mucosal biopsies or from directed differentiation of human pluripotent stem cells may constitute complementary treatment options for patients with mucosal damage, as intestinal epithelial stem cells are multipotent and may give rise to all epithelial cell types of the intestine. This review provides the reader with a comprehensive state-of-the-art overview of the intestinal barrier's role in healthy and diseased states, discussing the clinical application of stem cell-based approaches to accomplish mucosal healing in inflammatory bowel disease.
正常屏障功能的破坏是炎症性肠病发病机制的一个基本因素，包括上皮细胞死亡增加、黏液结构改变、紧密连接蛋白表达和分布改变，以及抗菌肽表达减少。炎症性肠病会使受影响的患者终生发病，其发病率和患病率在全球范围内都呈上升趋势，给社会带来了巨大的经济负担。黏膜愈合和屏障完整性的重建与临床缓解以及改善患者预后相关。因此，这些因素是至关重要的治疗目标，传统上通过一系列的医学治疗来实现，尽管这些治疗方法对所有患者都不是有效的，导致一些患者在某些时候仍需要手术。因此，有必要寻找新的治疗策略来实现黏膜愈合和重建炎症性肠病的正常屏障完整性，基于腔室干细胞的方法可能具有诱人的潜力。体外扩增的肠上皮干细胞可以直接从黏膜活检中获得，也可以从人类多能干细胞的定向分化中获得，它们可能成为黏膜损伤患者的补充治疗选择，因为肠上皮干细胞具有多能性，可以产生肠道的所有上皮细胞类型。本文为读者提供了一个关于肠道屏障在健康和疾病状态下作用的全面最新概述，讨论了基于干细胞的方法在炎症性肠病中实现黏膜愈合的临床应用。
