Age-Related Alterations in Regeneration of the Urinary Bladder after Subtotal Cystectomy

Burmeister, David M.; Aboushwareb, Tamer; Bergman, Christopher R.; Andersson, Karl‐Erik; Christ, George J.

doi:10.1016/j.ajpath.2013.07.018

Cited by 10 publications

(9 citation statements)

References 39 publications

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“…These show a high potential for neoregeneration of the all layers of the bladder wall. The urinary bladder in humans, canine, and rodent species possess a remarkable regenerative capacity of restoring both anatomy and functionality even after subtotal cystectomy . The similarities between species regarding bladder regeneration have made a small animal rodent model relevant for studying the molecular mechanisms involved in tissue repair and regeneration.…”

Section: Introductionmentioning

confidence: 99%

Molecular and histological studies of bladder wound healing in a rodent model

Chamorro

Engberg

Fossum

2020

Wound Repair Regeneration

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The field of regenerative medicine encounters different challenges. The success of tissue-engineered implants is dependent on proper wound healing. Today, the process of normal urinary bladder wound healing is poorly characterized. We aspired to explore and elucidate the natural response to injury in an in vivo model in order to further optimize tissue regeneration in future studies. In this study, we aimed to characterize histological and molecular changes during normal healing in a rat model by performing a standardized incisional wound followed by surgical closure. We used a rodent model (n = 40) to follow the healing process in the urinary bladder for 28 days. Surgical exposure of the bladder without incision (n = 40) was performed in controls. Histological characterization and western blot analyses of proteins was carried out using specific staining and markers for inflammation, proliferation, angiogenesis, and tissue maturation. For the molecular characterization of gene expression total RNA was collected for RT 2 -PCR in wound healing pathway arrays. Analysis of histology revealed distinct, but overlapping, phases of healing with a local inflammatory response (days 1-8) simultaneous with a rapid formation of granulation tissue and proliferation (days 2-8). We also identified significant changes in gene expression related to inflammation, proliferation, and extracellular matrix formation. Healing of an incisional wound in a rodent urinary bladder demonstrated that all the classical phases of wound healing: hemostasis, inflammation, proliferation followed by tissue maturation were present. Our data suggest that the bladder and the skin share similar molecular signaling during wound healing, although we noted differences in the duration of each phase compared to previous studies in rat skin. Further studies will address whether our findings can be extrapolated to the human bladder.

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Section: Introductionmentioning

confidence: 99%

Molecular and histological studies of bladder wound healing in a rodent model

Chamorro

Engberg

Fossum

2020

Wound Repair Regeneration

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“…Animals underwent trigone-sparing STC as previously described [ 21 , 22 , 42 ]. Briefly, two stay sutures were made on either side of the bladder, just above the uretero-vesical junction, using 6–0 polyglycolic acid.…”

Section: Methodsmentioning

confidence: 99%

“…Bladder catheters were implanted and cystometric studies were performed 3 days after catheter implantation in conscious, freely moving rats as previously described [ 21 , 42 , 43 ]. Briefly, the indwelling catheter was connected to a pressure transducer and infusion pump.…”

Section: Methodsmentioning

confidence: 99%

The potential utility of non-invasive imaging to monitor restoration of bladder structure and function following subtotal cystectomy (STC)

et al. 2015

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BackgroundRestoration of normal bladder volume and function (i.e., bioequivalent bladder) are observed within 8 weeks of performing subtotal cystectomy (STC; removal of ~70 % of the bladder) in 12-week old rats. For analysis of bladder function in rodents, terminal urodynamic approaches are largely utilized. In the current study, we investigated the potential for Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans to noninvasively track restoration of structure and function following STC.MethodsTwelve week old female Fisher F344 rats underwent STC and were scanned via CT and/or MRI 2, 4, 8, and 12 weeks post-STC, followed by urodynamic testing. After euthanasia, bladders were excised for histological processing.ResultsMRI scans demonstrated an initial decline followed by a time-dependent increase to normal bladder wall thickness (BWT) by 8 weeks post-STC. Masson’s trichrome staining showed a lack of fibrosis post-STC, and also revealed that the percent of smooth muscle in the bladder wall at 2 and 4 weeks positively correlated with pre-operative baseline BWT. Moreover, increased BWT values before STC was predictive of improved bladder compliance at 2 and 4 weeks post-STC. Cystometric studies indicated that repeated MRI manipulation (i.e. bladder emptying) apparently had a negative impact on bladder capacity and compliance. A “window” of bladder volumes was identified 2 weeks post-STC via CT scanning that were commensurate with normal micturition pressures measured in the same animal 6 weeks later.ConclusionsTaken together, the data indicate some limitations of “non-invasive” imaging to provide insight into bladder regeneration. Specifically, mechanical manipulation of the bladder during MRI appears to negatively impact the regenerative process per se, which highlights the importance of terminal cystometric studies.

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“…This is particularly true in cases where diseased bladder cannot be used due to the risk of cancer or advanced bladder decompensation and fibrosis [16,34,35]. The ability to develop an in vitro layer of urothelium onto grafts has been possible for some time [18].…”

Section: The Current State Of Autologous Bladder Tissue Engineeringmentioning

confidence: 99%

Future Perspectives in Bladder Tissue Engineering

Gill

Damaser

Chermansky

2015

Curr Bladder Dysfunct Rep

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Substantial clinical need persists for improved autologous tissues to augment or replace the urinary bladder and research has begun to address this using tissue engineering techniques. The implantation of both tissue scaffolds which allow for native bladder tissue ingrowth and autologous bladder grafts created from in vitro cellularization of such scaffolds have been tested clinically; however, successful outcomes in both scenarios have been challenged by insufficient vascularity resulting from large graft sizes, which subsequently limits tissue ingrowth and leads to central graft ischemia. Consequently, recent research has focused on developing better methods to produce scaffolds with increased tissue ingrowth and vascularity. This review provides an update on bladder tissue engineering and outlines the challenges that remain to clinical implementation.

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Age-Related Alterations in Regeneration of the Urinary Bladder after Subtotal Cystectomy

Cited by 10 publications

References 39 publications

Molecular and histological studies of bladder wound healing in a rodent model

Molecular and histological studies of bladder wound healing in a rodent model

The potential utility of non-invasive imaging to monitor restoration of bladder structure and function following subtotal cystectomy (STC)

Future Perspectives in Bladder Tissue Engineering

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