Mishra Rangnath, Dhawan Punita, Srivastava Anand S, Singh Amar B
Global Institute of Stem Cell Therapy and Research, San Diego, CA 92122, United States.
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68118, United States.
World J Stem Cells. 2020 Oct 26;12(10):1050-1066. doi: 10.4252/wjsc.v12.i10.1050.
Inflammatory bowel disease (IBD), consisting primarily of ulcerative colitis and Crohn's disease, is a group of debilitating auto-immune disorders, which also increases the risk of colitis-associated cancer. However, due to the chronic nature of the disease and inconsistent treatment outcomes of current anti-IBD drugs (, approximately 30% non-responders to anti-TNFα agents), and related serious side effects, about half of all IBD patients (in millions) turn to alternative treatment options. In this regard, mucosal healing is gaining acceptance as a measure of disease activity in IBD patients as recent studies have correlated the success of mucosal healing with improved prognosis. However, despite the increasing clinical realization of the significance of the concept of mucosal healing, its regulation and means of therapeutic targeting remain largely unclear. Here, stem-cell therapy, which uses hematopoietic stem cells or mesenchymal stem cells, remains a promising option. Stem cells are the pluripotent cells with ability to differentiate into the epithelial and/or immune-modulatory cells. The over-reaching concept is that the stem cells can migrate to the damaged areas of the intestine to provide curative help in the mucosal healing process. Moreover, by differentiating into the mature intestinal epithelial cells, the stem cells also help in restoring the barrier integrity of the intestinal lining and hence prevent the immunomodulatory induction, the root cause of the IBD. In this article, we elaborate upon the current status of the clinical management of IBD and potential role of the stem cell therapy in improving IBD therapy and patient's quality of life.
炎症性肠病(IBD)主要由溃疡性结肠炎和克罗恩病组成,是一组使人衰弱的自身免疫性疾病,还会增加结肠炎相关癌症的风险。然而,由于该疾病的慢性性质以及当前抗IBD药物的治疗效果不一致(约30%的患者对抗TNFα药物无反应),且存在相关严重副作用,约半数IBD患者(数百万计)转向替代治疗方案。在这方面,黏膜愈合作为衡量IBD患者疾病活动度的指标正逐渐被认可,因为最近的研究已将黏膜愈合的成功与改善的预后相关联。然而,尽管临床上越来越意识到黏膜愈合概念的重要性,但其调节机制和治疗靶点的手段仍 largely不清楚。在此,利用造血干细胞或间充质干细胞的干细胞疗法仍是一个有前景的选择。干细胞是具有分化为上皮细胞和/或免疫调节细胞能力的多能细胞。其核心概念是干细胞可迁移至肠道受损区域,在黏膜愈合过程中提供治愈性帮助。此外,通过分化为成熟的肠道上皮细胞,干细胞还有助于恢复肠黏膜的屏障完整性,从而防止免疫调节的诱导,而免疫调节诱导是IBD的根本原因。在本文中,我们阐述了IBD临床管理的现状以及干细胞疗法在改善IBD治疗和患者生活质量方面的潜在作用。