Ontogeny of interstitial cells of cajal in the human intestine

Background/Purpose: Interstitial cells of Cajal (ICC) recently have been id entified as intestinal pacemaker cells. Abnormalities in ICC are increasing ly recognized in a number of neonatal disorders such as infantile hypertrop hic pyloric stenosis, Hirschsprung's disease, and transient intestinal pseu do-obstruction. The aim of this study was to determine the fetal and postna tal differentiation and development of ICC in the human gastrointestinal tr act to aid interpretation of pathological specimens. Methods: Specimens of human gastrointestinal tract from (1) fetuses (9 to 1 7 weeks' gestation; n = 12), (2) premature and full-term neonates with non- gut motility-related disorders, (age 26 to 59 weeks' gestation; n = 13), an d (3) children (age 4 months to 13 years; n = 7) were immunohistochemically stained with antibodies to c-kit(a marker for ICC) and protein gene produc t 9.5 (PGP9.5, a marker for neu rat tissue). Results: (1) C-kit-positive ICC were present throughout the gut in all spec imens including those from the earliest gestational ages. C-kit and PGP9.5 immunoreactivities were present in different cell populations. (2) The dist ribution of ICC varied with gestational age and with region of the gut. (3) Maturation of ICC networks continues postnatally in a region-specific mann er. Conclusions: ICC are present from an early stage in human gut development. Interpretation of apparent abnormalities in ICC distribution as being of pa thological significance should be tempered by the knowledge that ICC networ ks continue to develop postnatally and that ICC development varies througho ut the gut. Copyright (C) 1999 by W.B. Saunders Company.