Regulation of intestinal epithelial homeostasis by mesenchymal cells

The gastrointestinal tract harbors diverse microorganisms in the lumen. Epithelial cells segregate the luminal microorganisms from immune cells in the lamina propria by constructing chemical and physical barriers through the production of various factors to prevent excessive immune responses against microbes. Therefore, perturbations of epithelial integrity are linked to the development of gastrointestinal disorders. Several mesenchymal stromal cell populations, including fibroblasts, myofibroblasts, pericytes, and myocytes, contribute to the establishment and maintenance of epithelial homeostasis in the gut through regulation of the self-renewal, proliferation, and differentiation of intestinal stem cells. Recent studies have revealed alterations in the composition of intestinal mesenchymal stromal cells in patients with inflammatory bowel disease and colorectal cancer. A better understanding of the interplay between mesenchymal stromal cells and epithelial cells associated with intestinal health and diseases will facilitate identification of novel biomarkers and therapeutic targets for gastrointestinal disorders. This review summarizes the key findings obtained to date on the mechanisms by which functionally distinct mesenchymal stromal cells regulate epithelial integrity in intestinal health and diseases at different developmental stages.