We were interested in the paper by Mutoh and colleagues¹ showing the development of epithelial intestinal metaplasia and mesenchymal proliferation in human stomach resections and Cdx2 transgenic mice. The authors used α smooth muscle actin (α-SMA) staining to mark periglandular fibroblasts and failed to show any α-SMA positive cells surrounding the en face glands of normal mouse and human stomach mucosa. In metaplastic tissue however, the periglandular fibroblast sheath was easily discernible, and the authors concluded that the fibroblast sheath was generated from the intestinal submucosa, possibly through expression of Cdx2.

Mesenchymal cells such as intestinal subepithelial myofibroblasts (ISEMF) are widely distributed. They are important coordinating cells that possess significant influence on their environment by virtue of their receptor profile and the signals they produce. Characteristically, ISEMF form a protective fenestrated sheath around the stem cell compartment, creating the stem cell niche—the optimal microenvironment for stem cells to give rise to differentiated …