Altered distribution of interstitial cells and innervation in the rat urinary bladder following spinal cord injury.

Changes in the distribution of interstitial cells (IC) are reportedly associated with dysfunctional bladder. This study investigated whether spinal cord injury (SCI) resulted in changes to IC subpopulations (vimentin-positive with the ultrastructural profile of IC), smooth muscle and nerves within the bladder wall and correlated cellular remodelling with functional properties. Bladders from SCI (T8/9 transection) and sham-operated rats 5 weeks post-injury were used for ex vivo pressure-volume experiments or processed for morphological analysis with transmission electron microscopy (TEM) and light/confocal microscopy. Pressure-volume relationships revealed low-pressure, hypercompliance in SCI bladders indicative of decompensation. Extensive networks of vimentin-positive IC were typical in sham lamina propria and detrusor but were markedly reduced post-SCI; semi-quantitative analysis showed significant reduction. Nerves labelled with anti-neurofilament and anti-vAChT were notably decreased post-SCI. TEM revealed lamina propria IC and detrusor IC which formed close synaptic-like contacts with vesicle-containing nerve varicosities in shams. Lamina propria and detrusor IC were ultrastructurally damaged post-SCI with retracted/lost cell processes and were adjacent to areas of cellular debris and neuronal degradation. Smooth muscle hypertrophy was common to SCI tissues. In conclusion, IC populations in bladder wall were decreased 5 weeks post-SCI, accompanied with reduced innervation, smooth muscle hypertrophy and increased compliance. These novel findings indicate that bladder wall remodelling post-SCI affects the integrity of interactions between smooth muscle, nerves and IC, with compromised IC populations. Correlation between IC reduction and a hypercompliant phenotype suggests that disruption to bladder IC contribute to pathophysiological processes underpinning the dysfunctional SCI bladder.

Ultrastructural properties of interstitial cells of Cajal in the Guinea pig bladder.

PURPOSE: We investigated the ultrastructural characteristics of interstitial cells of Cajal in the guinea pig bladder. MATERIALS AND METHODS: Bladders were removed from guinea pigs and processed for transmission electron microscopy. Some sections were labeled with c-Kit antibodies and colloidal gold particles for positive identification of interstitial cells of Cajal. RESULTS: Kit positive cells, identified with 10 nm gold particles, were located on the periphery of detrusor smooth muscle bundles and in the interbundle spaces. Interstitial cells of Cajal in these regions contained mitochondria, rough and smooth endoplasmic reticulum, thin and intermediate filaments, caveolae, Golgi apparatus, free ribosomes, cytoplasmic vesicles and had a discontinuous basal lamina. They were distinct from smooth muscle cells by an absence of dense bodies, membrane attachment bands and thick filaments. The ultrastructure of interstitial cells of Cajal in all regions of the bladder wall examined were similar and the myofibroblast characteristic, fibronexus, was not evident in any of the cells examined. Interstitial cells of Cajal had lateral branches which extended toward other interstitial cells of Cajal, neighboring smooth muscle cells or nerves. Cells with the ultrastructural profile of interstitial cells of Cajal were associated with bladder microvessels and their branched processes were in close proximity to vascular smooth muscle cells. CONCLUSIONS: Bladder interstitial cells of Cajal have typical ultrastructural characteristics of interstitial cells of Cajal from other tissues and were immunopositive for the interstitial cell of Cajal marker Kit. They were closely associated with detrusor smooth muscle and often networked with other interstitial cells of Cajal. The observation of perivascular cells with interstitial cells of Cajal characteristics indicates that there may be more subtypes of these cells in the bladder than previously considered.

Morphological expression of KIT positive interstitial cells of Cajal in human bladder.

PURPOSE: 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. MATERIALS AND 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.