Intestinal barrier integrity and inflammatory bowel disease: Stem cell‐based approaches to regenerate the barrier

Abstract

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.

Characterization and evolution of intestine injury at the anhepatic phase in portal hypertensive rats

“…The gastrointestinal tract is one of the target organs of I/R injury and is often described as the central organ of surgical stress and the initiating organ of multiple organ failure (24). The intestinal mucosa is rich in blood supply to ensure the absorption of nutrients and the maintenance of normal barrier function (25). Due to certain characteristics of intestinal villus oxygen exchange, including that the oxygen tension at the tip of villus is lower than that of the artery, cells have a high sensitivity to hypoxia and ischemia (26).…”

Emerging concepts in non-invasive monitoring of Crohn’s disease

“…Evidence is mounting for endothelial impairment contributing to the onset, progression and recovery from inflammatory injury. 135 , 136 Of particular interest, EPCs, derived from bone marrow hematopoietic stem cells, have the capability to migrate to the site of endothelial damage through the peripheral circulation. 137 Boltin and colleagues 137 studied patients with CD in varying stages of disease activity assessed using the CDAI.…”

Clinical Significance of CD147 in Children with Inflammatory Bowel Disease

“…Multiple studies have showed that inflammatory bowel disease (IBD) is a disorder of dysregulation by inflammation accompanied by impaired intestinal barrier function, which is an vital event in treatment of IBD [ 1 , 2 ]. The local inflammatory reaction is involved in the recruitment of various inflammatory cells and secretion of cytokines, including matrix metalloproteinases (MMPs), IL-1 β , and IL-6, which have a critical role in regulation of intestinal barrier function, thereby resulting in aggravating development of IBD.…”