Hepato-Gastroenterology Department, Claude Huriez hospital, University of Lille, Lille, France; Inserm Unit 995, Lille, France.
Translational Gastroenterology Research Unit, GIGA-R, University of Liège, Liège, Belgium; Department of Gastroenterology, Jiao Tong University Hospital, Shanghai, China.
Clin Gastroenterol Hepatol. 2019 Apr;17(5):847-856. doi: 10.1016/j.cgh.2018.06.043. Epub 2018 Aug 23.
BACKGROUND & AIMS: Despite significant advances in the treatment of Crohn's disease (CD), most patients still develop stricturing or penetrating complications that require surgical resections. We performed a systematic review of mechanisms and potential treatments for tissue damage lesions in CD patients.
We searched the PubMed, MBASE, and Cochrane databases from January 1960 to July 2017 for full-length articles on CD, fibrosis, damage lesions, mesenchymal stem cells, and/or treatment. We also searched published conference abstracts and performed manual searches of all reference lists of relevant articles.
Mechanisms of intestinal damage in patients with CD include fibroblast proliferation and migration, activation of stellate cells, recruitment of intestinal or extra-intestinal fibroblast, and cell trans-differentiation. An altered balance of metalloproteinases and tissue inhibitors of metalloproteinases might contribute to fistula formation. Treatment approaches that reduce excessive transforming growth factor beta (TGFB) activation might be effective in treating established intestinal damage. Stem cell therapies have been effective in tissue damage lesions in CD. Particularly, randomized controlled trials have shown local injections of mesenchymal stem cells to heal perianal fistulas.
In a systematic review of mechanisms and treatments of bowel wall damage in patients with CD, we found a need to test drugs that reduce TGFB and increase healing of transmural damage lesions and to pursue research on local injection of mesenchymal stem cells.
尽管克罗恩病（CD）的治疗取得了重大进展，但大多数患者仍会出现狭窄或穿透性并发症，需要进行手术切除。我们对 CD 患者组织损伤病变的机制和潜在治疗方法进行了系统评价。
我们检索了 1960 年 1 月至 2017 年 7 月期间 PubMed、MBASE 和 Cochrane 数据库中关于 CD、纤维化、损伤病变、间充质干细胞和/或治疗的全文文章。我们还检索了已发表的会议摘要，并对所有相关文章的参考文献进行了手工检索。
CD 患者肠道损伤的机制包括成纤维细胞增殖和迁移、星状细胞激活、肠内或肠外成纤维细胞募集和细胞转分化。金属蛋白酶和金属蛋白酶组织抑制剂的平衡改变可能导致瘘管形成。减少过度转化生长因子β（TGFB）激活的治疗方法可能对治疗已建立的肠道损伤有效。干细胞疗法在 CD 的组织损伤病变中有效。特别是，随机对照试验表明，局部注射间充质干细胞可治愈肛周瘘。
在对 CD 患者肠壁损伤的机制和治疗方法进行系统评价后，我们发现需要测试减少 TGFB 并增加透壁损伤病变愈合的药物，并对间充质干细胞的局部注射进行研究。
