Increased extracellular matrix stiffness accompanies compromised bladder function in a murine model of radiation cystitis

Zwaans, Bernadette; Grobbel, Marissa R.; Carabulea, Alexander L; Lamb, Laura E.; Roccabianca, Sara

doi:10.1016/j.actbio.2022.03.017

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…By using the histogram representation of the YM we identified stiffening of the urothelium 2 months after irradiation, suggesting that the main effect of irradiation was on the cells, which it is well known to induce cell apoptosis 28 , and apoptotic cells have been previously reported to be stiffer 29 . At the second studied time point, i.e., 4 months, stiffening of the lamina propria and muscle occurred, in agreement with a previous study 30 . The YM in 6-months irradiated animal did not change compared to the 4-months treated animal, while the mechanics of bladder in control animal increased from 4 to 6 months of age, masking the effect of the treatment.…”

Section: Discussionsupporting

confidence: 92%

Micro-mechanical fingerprints of the rat bladder change in actinic cystitis and tumor presence

et al. 2023

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Tissue mechanics determines tissue homeostasis, disease development and progression. Bladder strongly relies on its mechanical properties to perform its physiological function, but these are poorly unveiled under normal and pathological conditions. Here we characterize the mechanical fingerprints at the micro-scale level of the three tissue layers which compose the healthy bladder wall, and identify modifications associated with the onset and progression of pathological conditions (i.e., actinic cystitis and bladder cancer). We use two indentation-based instruments (an Atomic Force Microscope and a nanoindenter) and compare the micromechanical maps with a comprehensive histological analysis. We find that the healthy bladder wall is a mechanically inhomogeneous tissue, with a gradient of increasing stiffness from the urothelium to the lamina propria, which gradually decreases when reaching the muscle outer layer. Stiffening in fibrotic tissues correlate with increased deposition of dense extracellular matrix in the lamina propria. An increase in tissue compliance is observed before the onset and invasion of the tumor. By providing high resolution micromechanical investigation of each tissue layer of the bladder, we depict the intrinsic mechanical heterogeneity of the layers of a healthy bladder as compared with the mechanical properties alterations associated with either actinic cystitis or bladder tumor.

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Section: Discussionsupporting

confidence: 92%

Micro-mechanical fingerprints of the rat bladder change in actinic cystitis and tumor presence

et al. 2023

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“…The 40 Gy dose has the advantage of inducing vascular lesions without causing deleterious lesions for the animal, unlike higher doses. This dose is consistent with the literature where it is described to induce CRC [25,40,41,44,45], justifying the 40 Gy dose for the MSC study.…”

Section: Discussionsupporting

confidence: 89%

Mesenchymal stem cells limit vascular and epithelial damage and restore the impermeability of the urothelium in chronic radiation cystitis

et al. 2023

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Background Cellular therapy seems to be an innovative therapeutic alternative for which mesenchymal stem cells (MSCs) have been shown to be effective for interstitial and hemorrhagic cystitis. However, the action of MSCs on chronic radiation cystitis (CRC) remains to be demonstrated. The aim of this study was to set up a rat model of CRC and to evaluate the efficacy of MSCs and their mode of action. Methods CRC was induced by single-dose localized irradiation of the whole bladder using two beams guided by tomography in female Sprague–Dawley rat. A dose range of 20–80 Gy with follow-up 3–12 months after irradiation was used to characterize the dose effect and the kinetics of radiation cystitis in rats. For the treatment, the dose of 40 Gy was retained, and in order to potentiate the effect of the MSCs, MSCs were isolated from adipose tissue. After expansion, they were injected intravenously during the pre-chronic phase. Three injections of 5 million MSCs were administered every fortnight. Follow-up was performed for 12 months after irradiation. Results We observed that the intensity and frequency of hematuria are proportional to the irradiation dose, with a threshold at 40 Gy and the appearance of bleeding from 100 days post-irradiation. The MSCs reduced vascular damage as well as damage to the bladder epithelium. Conclusions These results are in favor of MSCs acting to limit progression of the chronic phase of radiation cystitis. MSC treatment may afford real hope for all patients suffering from chronic radiation cystitis resistant to conventional treatments.

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“…These data were also used to derive biomechanical metrics, as described previously (Tuttle et al 2022 ; Zwaans et al 2022 ). Briefly, we define E low and E high as the slope of the spherical stress-stretch curve for low and high values of pressure, respectively.…”

Section: Methodsmentioning

confidence: 99%

Quantifying whole bladder biomechanics using the novel pentaplanar reflected image macroscopy system

Hennig

Saxena

Broemer

et al. 2023

Biomech Model Mechanobiol

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Optimal bladder compliance is essential to urinary bladder storage and voiding functions. Calculated as the change in filling volume per change in pressure, bladder compliance is used clinically to characterize changes in bladder wall biomechanical properties that associate with lower urinary tract dysfunction. But because this method calculates compliance without regard to wall structure or wall volume, it gives little insight into the mechanical properties of the bladder wall during filling. Thus, we developed Pentaplanar Reflected Image Macroscopy (PRIM): a novel ex vivo imaging method to accurately calculate bladder wall stress and stretch in real time during bladder filling. The PRIM system simultaneously records intravesical pressure, infused volume, and an image of the bladder in five distinct visual planes. Wall thickness and volume were then measured and used to calculate stress and stretch during filling. As predicted, wall stress was nonlinear; only when intravesical pressure exceeded ~ 15 mmHg did bladder wall stress rapidly increase with respect to stretch. This method of calculating compliance as stress vs stretch also showed that the mechanical properties of the bladder wall remain similar in bladders of varying capacity. This study demonstrates how wall tension, stress and stretch can be measured, quantified, and used to accurately define bladder wall biomechanics in terms of actual material properties and not pressure/volume changes. This method is especially useful for determining how changes in bladder biomechanics are altered in pathologies where profound bladder wall remodeling occurs, such as diabetes and spinal cord injury.

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Increased extracellular matrix stiffness accompanies compromised bladder function in a murine model of radiation cystitis

Cited by 9 publications

References 33 publications

Micro-mechanical fingerprints of the rat bladder change in actinic cystitis and tumor presence

Micro-mechanical fingerprints of the rat bladder change in actinic cystitis and tumor presence

Mesenchymal stem cells limit vascular and epithelial damage and restore the impermeability of the urothelium in chronic radiation cystitis

Quantifying whole bladder biomechanics using the novel pentaplanar reflected image macroscopy system

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