INTERSTITIAL-CELLS OF CAJAL IN HUMAN COLON AND IN HIRSCHSPRUNGS-DISEASE

Background & Aims: Subpopulations of interstitial cells of Cajal are r egarded as the source of spontaneous slow waves of the gut musculature (pacemaker cells), Their ontogeny remains unclear, but a role of the tyrosine kinase receptor c-kit in their development has recently been recognized, This study examined the interstitial cells in the human co lon and in Hirschsprung's disease (aganglionosis), Methods: The distri bution of the c-kit receptor was studied using specific antibodies in 5 normal patients, 10 patients with Hirschsprung's disease, and 3 pati ents with diversion loop enterostomies, c-kit immunohistochemistry was also combined with reduced nicotinamide adenine dinucleotide phosphat e diaphorase histochemistry or with c-kit ligand (stem cell factor) im munohistochemistry. Transmission electron microscopy was performed in 1 patient with Hirschsprung's disease, Results: c-kit immunoreactivity labeled a network of interstitial cells at the outer edge of the subm ucosa, in the muscular layers, and around the myenteric plexus, In aga nglionic segments, interstitial cells were scarce and its network appe ared disrupted, Interstitial cells of Cajal were identified in agangli onic regions by electron microscopy, Interstitial cells of Cajal are i dentifiable in newborns and exhibit similar distribution in diversion loops independent of contact with luminal nutrients, Conclusions: Our morphological data may explain the abnormal spontaneous electrical act ivity in aganglionic segments of Hirschsprung's disease and may give n ew insight into the ontogeny of interstitial cells.