Mechanosensitivity Is a Characteristic Feature of Cultured Suburothelial Interstitial Cells of the Human Bladder

Abstract

Bladder dysfunction is characterized by urgency, frequency (pollakisuria, nocturia), and dysuria and may lead to urinary incontinence. Most of these symptoms can be attributed to disturbed bladder sensitivity. There is growing evidence that, besides the urothelium, suburothelial interstitial cells (suICs) are involved in bladder afferent signal processing. The massive expansion of the bladder during the filling phase implicates mechanical stress delivered to the whole bladder wall. Little is known about the reaction of suICs upon mechanical stress. Therefore, we investigated the effects of mechanical stimulation in cultured human suICs. We used fura-2 calcium imaging as a major physiological readout. We found spontaneous intracellular calcium activity in 75 % of the cultured suICs. Defined local pressure application via a glass micropipette led to local increased calcium activity in all stimulated suICs, spreading over the whole cell. A total of 51% of the neighboring cells in a radius of up to 100 µm from the stimulated cell showed an increased activity. Hypotonic ringer and shear stress also induced calcium transients. We found an 18-times increase in syncytial activity compared to unstimulated controls, resulting in an amplification of the primary calcium signal elicited in single cells by 50%. Our results speak in favor of a high sensitivity of suICs for mechanical stress and support the view of a functional syncytium between suICs, which can amplify and distribute local stimuli. Previous studies of connexin expression in the human bladder suggest that this mechanism could also be relevant in normal and pathological function of the bladder in vivo.

Telocytes and Other Interstitial Cells: From Structure to Function

“…Bladder dysfunction might be attributed to suburothelial interstitial cells, which can act as connecting devices between the urothelium and detrusor muscle. The original paper of Neuhaus et al, describing the mechanosensitivity of suburothelial interstial cells from the human bladder focused on calcium transients detected in cultivated cells stimulated by various mechanical stimuli [ 4 ]. The authors propose a mechanism of non-neuronal signaling in the human bladder intermediated by a network of interstitial mesenchymal cells that occupy a strategic position between the urothelial layer and the deep lamina propria and express specific receptors and connexin Cx43, leading to the formation of a functional syncytium [ 4 ].…”

Functional Expression of Transient Receptor Potential and Piezo1 Channels in Cultured Interstitial Cells of Human-Bladder Lamina Propria

“…Then, small fragments (∼1 mm 2 ) were digested with trypsin in 37 • C for 15 min, and digestion was stopped by 10% fetal bovine serum. Then, tissue was plated into tissue culture flasks for incubation in an atmosphere of 5% CO 2 at 37 • C. Smooth Muscle Cell Growth Medium 2 (Procell, Wuhan, China) was used as the culture medium to limit the growth of urothelial cells (Neuhaus et al, 2020). Cells from passage-2 to passage-8 were used.…”

Scoping review and interpretation of Myofascial Pain/Fibromyalgia syndrome: an attempt to assemble a medical puzzle

“…It is shown myo/fibroblasts have gap junctions that can couple and directly communicate with each other (Xu et al 2021) 237 and with other types of cells (with heart, 238 hair follicles, 239 cancer cells, 240 etc.) [241][242][243][244] and these can contract as a unit or in patterns, 244,245 affecting the organ's functionality. [246][247][248][249][250][251][252][253][254][255][256][257][258] If this theoretical model of "fascial armoring" is verified empirically, it might be worth further exploring the possibility that they can couple in vivo (directly, or indirectly through myocytes/glial cells) to nerves.…”

“…[259][260][261][262] Studies suggest the myodural bridge connects the extracranial occipital fascia with the dura. 263 Myo/fibroblasts seem to form a body-wide cellular network that can respond to mechanical cues and exhibit spontaneous calcium oscillations and synchronized contractions, 245,[264][265][266][267] and fibroblast themselves can induce contracture through actin beta and gamma pathways. 268 We could consider the hypothetical possibility that this dynamic body-wide mechanoelectrical network of cells and fibers has an overlooked interplay with the network of the human nervous system.…”