Telocytes subtypes in human urinary bladder

Abstract

Urinary bladder voiding is a complex mechanism depending upon interplay among detrusor, urothelium, sensory and motor neurons and con-nective tissue cells. The identity of some of the latter cells is still controversial. We presently attempted to clarify their phenotype(s) in the human urinary bladder by transmission electron microscopy (TEM) and immunohistochemistry. At this latter aim, we used CD34, PDGFRa, aSMA, c-Kit and calreticulin antibodies. Both, TEM and immunohistochemistry, showed cells that, sharing several telocyte (TC) characteristics, we identified as TC; these cells, however, differed from each other in some ultrastructural features and immunolabelling according to their loca-tion. PDGFRa/calret-positive, CD34/c-Kit-negative TC were located in the sub-urothelium and distinct in two subtypes whether, similarly to myo-fibroblasts, they were aSMA-positive and had attachment plaques. The sub-urothelial TC formed a mixed network with myofibroblasts and were close to numerous nerve endings, many of which nNOS-positive. A third TC subtype, PDGFRa/aSMA/c-Kit-negative, CD34/calret-positive, ultra-structurally typical, was located in the submucosa and detrusor. Briefly, in the human bladder, we found three TC subtypes. Each subtype likely forms a network building a 3-D scaffold able to follow the bladder wall distension and relaxation and avoiding anomalous wall deformation. The TC located in the sub-urothelium, a region considered a sort of sensory system for the micturition reflex, as forming a network with myofibro-blasts, possessing specialized junctions with extracellular matrix and being close to nerve endings, might have a role in bladder reflexes. In con-clusions, the urinary bladder contains peculiar TC able to adapt their morphology to the organ activity