Interstitial cells of Cajal in the normal gut and in intestinal motility disorders of childhood

Abstract

Interstitial cells of Cajal (ICCs) are pacemaker cells which are densely distributed throughout the whole gastrointestinal tract. ICCs have important functions in neurotransmission, generation of slow waves and regulation of mechanical activities in the gastrointestinal tract, especially for the coordinated gastrointestinal peristalsis. Therefore, a loss of ICCs could result in gastrointestinal motor dysfunction. In recent years c-kit labeling has been widely used to study pathological changes of ICCs in gastrointestinal motility disorders. Paediatric gastrointestinal motility disorders such as hypertrophic pyloric stenosis, Hirschsprung's disease, total colonic aganglionosis, hypoganglionosis, intestinal neuronal dysplasia, internal anal sphincter achalasia, megacystis microcolon intestinal hypoperistalsis syndrome have been reported to be associated with loss or deficiency of ICCs networks. This review describes the distribution of ICCs in the normal gastrointestinal tract and its altered distribution in intestinal motility disorders of childhood.

Absence of the interstitial cells of Cajal in a child with chronic pseudoobstruction

“…In a number of gastrointestinal disorders including infantile hypertrophic pyloric stenosis, Hirschsprung's disease, and achalasia, the distribution of ICC appears to be reduced and/or abnormal, making them a promising target for future pharmacological interventions [6,12,13]. Absence of ICCs has been suggested to be a causative factor leading to intestinal pseudoobstruction in adults [3,13].…”

“…Second, ICCs mediate inhibitory and excitatory motor neurotransmission by the enteric nervous system. They achieve this by playing a critical role in reception and transduction [6,10,11].…”

“…This specification is important because not all ICCs have the same role in gastrointestinal motility [3,6,9]. Two major functions have been ascribed to the ICCs.…”

“…C-kit is expressed by ICCs and is stimulated by its natural ligand, stem cell factor (C-kit ligand or mast cell growth factor). Most believe the signaling pathway between stem cell factor and C-kit is essential for the initial development of ICCs and is crucial for postnatal proliferation and maintenance of ICCs [3][4][5][6][7][8].…”

Advances in Research on Pacemaking Function of Interstitial Cell of Cajal in Gastrointestinal Tract

“…In humans, under certain pathophysiological conditions, loss or defects in ICC networks appear to play a role in the generation of certain motility disorders (Vanderwinden et al, 1999;Horisawa et al, 1998). Recent evidence suggests that loss of ICC is associated with numerous gastrointestinal disorders ranging from gastroparesis, pseudoobstruction and idiopathic constipation (Vanderwinden et al, 1999;Sanders et al, 1999;Burns et al, 2007;Rolle et al, 2007;Farrugia et al, 2008). An animal model of ICC loss, the W/WV mouse, has been used extensively to examine functional changes resulting from lesions in ICC (Maeda et al, 1992;Ward et al, 1994;.…”