Identification of interstitial cells of Cajal in human urinary bladder: Concept of vesical pacemaker

Objectives. To determine whether, given the presence of interstitial cells of Cajal (ICCs) in organs that discharge slow waves, such as the gastrointestinal tract, such cells could also be present in the human urinary bladder (UB) and might exist in great numbers in the bladder dome, constituting the "primary pacemaker" from which slow waves spread to the body of the UB. This hypothesis was based on previous studies that had demonstrated the vesical electric waves starting in the dome and spreading caudad. Methods. Specimens (0.5 x 0.5 cm) from different vesical locations were obtained from the cystectomized UB of 18 patients (12 men, 6 women, mean age 42.6 +/- 3.8 years) with bladder cancer. Fixed sections were prepared and subjected to c-kit immunohistochemistry. Controls for the antiserum specificity consisted of incubation of the tissue with normal rabbit serum substituted for the primary antiserum. Results. Fusiform, c-kit positive, and ICC-like cells were detected in the vesical muscle layers; they had dendritic processes. They occurred separately or were connected through the dendritic processes to form a cellular network. An accumulation of ICCs surrounded by a connective tissue layer was detected in all the dome specimens. Mast cells occurred in the vesical mucosa and submucosa; they were c-kit positive but had a rounded body with no dendritic processes. Conclusions. We identified cells in the UB with morphologic and immunologic phenotypes similar to the ICCs of the gut. An accumulation of these cells, detected in the vesical dome, seems to constitute the "primary" vesical pacemaker that initiates the slow waves that spread to the other vesical walls. We believe that a deficiency or absence of these cells may be involved in vesical motility disorders. Additional studies are needed to delineate the role of these cells in UB physiology and pathologic conditions. (C) 2004 Elsevier Inc.