Absence of Interstitial Cells of Cajal in Human Colonic Muscularis Mucosae: Implications for Mucosal Motility Control

Interstitial cells of Cajal (ICC) are specialized pacemaker cells essential for gastrointestinal motility, generating electrical slow waves and mediating neurotransmission between enteric nerves and smooth muscle. While ICC have been characterized in the tunica muscularis, ICC in the lamina muscularis mucosae (ICC-MM) remain poorly studied in the human colon. Abnormal muscularis mucosae motor activity is associated with inflammatory bowel diseases and functional disorders, making ICC-MM characterization clinically relevant. This retrospective study examined 15 archived paraffin-embedded human colon specimens using immunohistochemistry. Primary antibodies included CD117/c-kit (established ICC marker) and CD31. Microscopic examination focused on identifying ICC-MM based on characteristic spindle-shaped, stellate, or polygonal morphology with c-kit immunoreactivity in the muscularis mucosae region. ICC-MM were not evident in any examined specimens; c-kit immunostaining revealed only scattered round-to-oval cells with granular cytoplasm, identified as mast cells based on morphology and perivascular distribution. No distinct, strongly positive spindle-shaped, stellate, or polygonal cells characteristic of ICC were observed in the muscularis mucosae. CD31 staining confirmed normal endothelial distribution. The absence of ICC-MM in human colonic muscularis mucosae suggests that mucosal motility relies on direct neural innervation rather than ICC-mediated pacemaker activity. This fundamental difference from other gastrointestinal layers has important implications for understanding functional bowel disorders and may explain the variable efficacy of ICC-targeted therapies in colonic motility disorders. The muscularis mucosae should be considered a distinct therapeutic target that warrants distinct approaches.