Morphological expression of KIT positive interstitial cells of Cajal in human bladder.
OBJECTIVE
We investigated the 3-dimensional morphological arrangement of KIT positive interstitial cells of Cajal in the human bladder and explored their structural interactions with neighboring cells.


METHODS
Human bladder biopsy samples were prepared for immunohistochemistry/confocal or transmission electron microscopy.


RESULTS
Whole mount, flat sheet preparations labeled with anti-KIT (Merck, Darmstadt, Germany) contained several immunopositive interstitial cell of Cajal populations. A network of stellate interstitial cells of Cajal in the lamina propria made structural connections with a cholinergic nerve plexus. Vimentin positive cells of several morphologies were present in the lamina propria, presumably including fibroblasts, interstitial cells of Cajal and other cells of mesenchymal origin. Microvessels were abundant in this region and branched, elongated KIT positive interstitial cells of Cajal were found discretely along the vessel axis with each perivascular interstitial cell of Cajal associated with at least 6 vascular smooth muscle cells. Detrusor interstitial cells of Cajal were spindle-shaped, branched cells tracking the smooth muscle bundles, closely associated with smooth muscle cells and vesicular acetylcholine transferase nerves. Rounded, nonbranched KIT positive cells were more numerous in the lamina propria than in the detrusor and were immunopositive for anti-mast cell tryptase. Transmission electron microscopy revealed cells with the ultrastructural characteristics of interstitial cells of Cajal throughout the human bladder wall.


CONCLUSIONS
The human bladder contains a network of KIT positive interstitial cells of Cajal in the lamina propria, which make frequent connections with a cholinergic nerve plexus. Novel perivascular interstitial cells of Cajal were discovered close to vascular smooth muscle cells, suggesting interstitial cells of Cajal-vascular coupling in the bladder. KIT positive detrusor interstitial cells of Cajal tracked smooth muscle bundles and were associated with nerves, perhaps showing a functional tri-unit controlling bladder contractility.
Johnston
Louise
L
Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast and Department of Urology, Belfast City Hospital, Belfast, United Kingdom.
Woolsey
Siobhan
S
Cunningham
Rebecca M J
RM
O'Kane
Hugh
H
Duggan
Brian
B
Keane
Patrick
P
McCloskey
Karen D
KD
D001706:Biopsy; D006801:Humans; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000378:metabolism*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009092:Mucous Membrane / Q000166:cytology; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D001743:Urinary Bladder / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism*
D019009:Proto-Oncogene Proteins c-kit