Abstract
BACKGROUND & AIMS: Subpopulations of interstitial cells of Cajal are regarded 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 colon and in Hirschsprung's disease (aganglionosis). METHODS: The distribution of the c-kit receptor was studied using specific antibodies in 5 normal patients, 10 patients with Hirschsprung's disease, and 3 patients with diversion loop enterostomies. c-kit immunohistochemistry was also combined with reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry or with c-kit ligand (stem cell factor) immunohistochemistry. 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 submucosa, in the muscular layers, and around the myenteric plexus. In aganglionic segments, interstitial cells were scarce and its network appeared disrupted. Interstitial cells of Cajal were identified in aganglionic regions by electron microscopy. Interstitial cells of Cajal are identifiable 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 activity in aganglionic segments of Hirschsprung's disease and may give new insight into the ontogeny of interstitial cells. (Gastroenterology 1996 Oct;111(4):901-10)
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