Ontogeny of interstitial cells of Cajal in the human intestine.
OBJECTIVE
Interstitial cells of Cajal (ICC) recently have been identified as intestinal pacemaker cells. Abnormalities in ICC are increasingly recognized in a number of neonatal disorders such as infantile hypertrophic pyloric stenosis, Hirschsprung's disease, and transient intestinal pseudo-obstruction. The aim of this study was to determine the fetal and postnatal differentiation and development of ICC in the human gastrointestinal tract to aid interpretation of pathological specimens.


METHODS
Specimens of human gastrointestinal tract from (1) fetuses (9 to 17 weeks' gestation; n = 12), (2) premature and full-term neonates with non-gut motility-related disorders, (age 26 to 59 weeks' gestation; n = 13), and (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 product 9.5 (PGP9.5, a marker for neural tissue).


RESULTS
(1) C-kit-positive ICC were present throughout the gut in all specimens including those from the earliest gestational ages. C-kit and PGP9.5 immunoreactivities were present in different cell populations. (2) The distribution of ICC varied with gestational age and with region of the gut. (3) Maturation of ICC networks continues postnatally in a region-specific manner.


CONCLUSIONS
ICC are present from an early stage in human gut development. Interpretation of apparent abnormalities in ICC distribution as being of pathological significance should be tempered by the knowledge that ICC networks continue to develop postnatally and that ICC development varies throughout the gut.
Kenny
S E
SE
Department of Paediatric Surgery and University of Liverpool, Alder Hey Children's Hospital, England, UK.
Connell
G
G
Woodward
M N
MN
Lloyd
D A
DA
Gosden
C M
CM
Edgar
D H
DH
Vaillant
C
C
D002648:Child; D002675:Child, Preschool; D004064:Digestive System / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D005769:Gastrointestinal Motility / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis
D019009:Proto-Oncogene Proteins c-kit