Characterization of interstitial Cajal progenitors cells and their changes in Hirschsprung's disease.
Interstitial cells of Cajal (ICC) are critical to gastrointestinal motility. The phenotypes of ICC progenitors have been observed in the mouse gut, but whether they exist in the human colon and what abnormal changes in their quantity and ultrastructure are present in Hirschsprung's disease (HSCR) colon remains uncertain. In this study, we collected the surgical resection of colons, both proximal and narrow segments, from HSCR patients and normal controls. First, we identified the progenitor of ICC in normal adult colon using immunofluorescent localization techniques with laser confocal microscopy. Next, the progenitors were sorted to observe their morphology. We further applied flow cytometry to examine the content of ICC progenitors in these fresh samples. The ultrastructural changes in the narrow and proximal parts of the HSCR colon were observed using transmission electron microscopy (TEM) and were compared with the normal adult colon. The presumed early progenitor (c-Kit(low)CD34(+)Igf1r(+)) and committed progenitor (c-Kit(+)CD34(+)Igf1r(+)) of ICC exist in adult normal colon as well as in the narrow and proximal parts of the HSCR colon. However, the proportions of mature, early and committed progenitors of ICC were dramatically reduced in the narrow segment of the HSCR colon. The proportions of mature and committed progenitors of ICC in the proximal segment of the HSCR colon were lower than in the adult normal colon. Ultrastructurally, ICC, enteric nerves, and smooth muscle in the narrow segment of the HSCR colon showed severe injury, including swollen vacuola or ted mitochondria, disappearance of mitochondrial cristae, dilated rough endoplasmic reticulum, vesiculation and degranulation, and disappearance of the caveolae on the ICC membrane surface. The contents of ICC and its progenitors in the narrow part of the HSCR colon were significantly decreased than those of adult colon, which may be associated with HSCR pathogenesis.
Shanghai Institute for Pediatric Research, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
Zhi-Hua
ZH
Chen
The 32 Ward of Oncology, Hunan Provincial Tumor Hospital, the Affiliated Tumor Hospital of Xiang Ya Medical School of Central University, Changsha, P. R. China.
Yong-Chang
YC
Zhang
Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P. R. China.
Wei-Fang
WF
Jiang
Stanford University School of Medicine, Stanford, California, United States of America.
Cissy
C
Yang
Shanghai Institute for Pediatric Research, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
Gang-Ming
GM
Zou
Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P. R. China.
Yu
Y
Kong
Shanghai Institute for Pediatric Research, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
Wei
W
Cai
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D006627:Hirschsprung Disease / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D056885:Interstitial Cells of Cajal / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D032390:Myoblasts, Smooth Muscle / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype