Intestinal stem cells and celiac disease

Abstract

Stem cells (SCs) are the key to tissue genesis and regeneration. Given their central role in homeostasis, dysfunctions of the SC compartment play a pivotal role in the development of cancers, degenerative disorders, chronic inflammatory pathologies and organ failure. The gastrointestinal tract is constantly exposed to harsh mechanical and chemical conditions and most of the epithelial cells are replaced every 3 to 5 d. According to the so-called Unitarian hypothesis, this renewal is driven by a common intestinal stem cell (ISC) residing within the crypt base at the origin of the crypt-to-villus hierarchical migratory pattern. Celiac disease (CD) can be defined as a chronic immune-mediated disease that is triggered and maintained by dietary proteins (gluten) in genetically predisposed individuals. Many advances have been achieved over the last years in understanding of the pathogenic interactions among genetic, immunological and environmental factors in CD, with a particular emphasis on intestinal barrier and gut microbiota. Conversely, little is known about ISC modulation and deregulation in active celiac disease and upon a gluten-free diet. Nonetheless, bone marrow-derived SC transplantation has become an option for celiac patients with complicated or refractory disease. This manuscript summarizes the “state of the art” regarding CD and ISCs, their niche and potential role in the development and treatment of the disease.

Keywords: Intestinal stem cells; CD133; Lgr5; Celiac disease; Paneth cells; Gut microbiota; Gut barrier

Core tip: The intestinal epithelium has a high turnover rate since most of the epithelial cells are replaced every 3 to 5 d. This renewal is driven by intestinal stem cells residing within the crypt base at the origin of the crypt-to-villus hierarchical migratory pattern. Many aspects of the pathogenesis of celiac disease have been elucidated over the last years regarding the interactions among genetic and immunological factors, intestinal barrier and gut microbiota. Conversely, little is known about intestinal stem cell modulation and deregulation in celiac disease. The current knowledge regarding celiac disease and intestinal stem cells, and the potential role of stem cells in the development and treatment of the disease are summarized.

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