Inflammatory bowel disease: Therapeutic limitations and prospective of the stem cell therapy

Abstract

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 (e.g., 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.

Keywords: Crohn′s disease; Hematopoietic stem cells; Mesenchymal stem cells; Mucosal healing; Ulcerative colitis.

Figure 1

The mucosal lining in a healthy intestine is maintained intact which helps limit bacterial population in gut itself.

Figure 2

The mucosal lining of the intestine is disrupted due to prolonged local inflammation and thus allowing migration of gut bacteria into intestinal tissues. Stem cells by virtue of having immune modulatory capabilities down-regulate local inflammation, and because of ability to migrate and settle in injured tissues can migrate to damaged regions of intestines, settle there and differentiate into cell types of immediate surrounding to help in mucosal healing.