Nerve distribution in rat urinary bladder after incorporation of acellular matrix graft or subtotal cystectomy

Frederiksen, Hans Jørgen; Davidsson, Thomas; Gabella, Giorgio; Uvelius, Bengt

doi:10.1080/00365590701871641

Cited by 7 publications

(8 citation statements)

References 29 publications

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“…23 A later study by this group demonstrated that the nerves of the well-innervated regenerated bladder had originated from preexisting nerves in the detrusor. 24 Although these studies do provide some insight into the regeneration of the bladder following STC, the process remains not fully understood. To this end, we report herein our use of a rodent model to examine the early stages of in situ bladder regeneration that occurs following STC.…”

Section: Discussionmentioning

confidence: 99%

Early Stages of In Situ Bladder Regeneration in a Rodent Model

Burmeister

Aboushwareb

Tan

et al. 2010

Tissue Engineering Part A

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Surgical removal of approximately 70% of the bladder (subtotal cystectomy [STC]) was used as a model system to gain insight into the normal regenerative process in adult mammals in vivo. Female F344 rats underwent STC, and at 2, 4, and 8 weeks post-STC, bladder regeneration was monitored via microcomputed tomography scans, urodynamic (bladder function studies) pharmacologic studies, and immunohistochemistry. Computed tomography imaging revealed a time-dependent increase in bladder size at 2, 4, and 8 weeks post-STC, which positively correlated with restoration of bladder function. Bladders emptied completely at all time points studied. The maximal contractile response to pharmacological activation and electrical field stimulation increased over time in isolated tissue strips from regenerating bladders, but remained lower at all time points compared with strips from age-matched control bladders. Immunostaining of the bladder wall of STC rats suggested a role for progenitor cells and cellular proliferation in the regenerative response. Immunostaining and the presence of electrical field stimulation-induced contractile responses verified innervation of the regenerated bladder. These initial studies establish the utility of the present model system for studying de novo tissue regeneration in vivo and may provide guidance with respect to optimization of intrinsic regenerative capacity for clinical applications.

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Section: Discussionmentioning

confidence: 99%

Early Stages of In Situ Bladder Regeneration in a Rodent Model

Burmeister

Aboushwareb

Tan

et al. 2010

Tissue Engineering Part A

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“…These well established observations regarding liver re-growth stand in contrast to rodent bladder regeneration, which occurs over a longer time frame (8 weeks rather than 2 weeks), and moreover, results in a regenerated bladder that structurally and functionally is essentially identical to the native bladder which it replaced [14], [15], [16]. More specifically, the bladder capacity and bladder wall thickness (as well as the presence of all three layers; urothelium, muscularis propria and lamina propria) of the regenerated bladder are indistinguishable from the previous native bladder, and moreover, the animals are entirely continent [14].…”

Section: Introductionmentioning

confidence: 95%

Characterization of the Early Proliferative Response of the Rodent Bladder to Subtotal Cystectomy: A Unique Model of Mammalian Organ Regeneration

et al. 2012

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Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder) elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU). Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP), muscularis propria (MP) and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA), to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh), Gli-1 and bone morphogenic factor-4 (BMP-4) were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends previous observations and further establishes the rodent bladder as an excellent model for studying novel aspects of mammalian organ regeneration.

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“…Researches on SIS have showed that it induces ingrowth of urothelium cells, smooth muscle cells, endothelial cells, and nerve tissues into SIS from adjacent bladder native parenchyma and improves bladder function after bladder augmentation. [2][3][4][5][6][7][8] In these researches, the bioactive factors of extracellular matrix preserved in the SIS might have important signal and regulatory functions in the development, maintenance, and regeneration of bladder tissues. 9,10 The list of the bioactive factors in the extracellular matrix is extremely extensive, which makes it very difficult for biomaterials scientists to detect each of them.…”

Section: Introductionmentioning

confidence: 99%

In vitro evaluation of the bioactive factors preserved in porcine small intestinal submucosa through cellular biological approaches

Yang¹,

Zhou²,

Sun³

et al. 2009

J Biomedical Materials Res

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The objective of this study was to develop cellular biological approaches to evaluate the potential effect of bioactive factors in porcine small intestinal submucosa (SIS) on bladder regeneration and angiogenesis. For this purpose, we cultured human bladder smooth muscle cell (HBSMC) and human umbilical vein endothelial cell (HUVEC), and then used cellular biological techniques to characterize in vitro biological effect of SIS components on HBSMC and HUVEC. Our results indicated that the SIS components had stimulated the attachment, proliferation, and migration of HBSMC and HUVEC, as well as tube formation by HUVEC on Matrigel. These results implied that the SIS might have preserved a mixture of bioactive factors including cell adhesion factors, mitogenic factors, chemotactic cytokines, and angiogenic factors, and these bioactive factors would have the potential of promoting bladder regeneration and angiogenesis. In conclusion, these cellular biological approaches might be helpful and effective for evaluation of the bioactive factors preserved in porcine SIS before it is used for bladder augmentation in humans.

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Nerve distribution in rat urinary bladder after incorporation of acellular matrix graft or subtotal cystectomy

Abstract: The nerves in the matrix grafts and the regrown parts of the subtotally cystectomized bladders derive from preexisting nerves in the bladder. In neither case does the nerve trunk or muscle bundle arrangement fully attain the pattern found in normal bladders.

Cited by 7 publications

References 29 publications

Early Stages of In Situ Bladder Regeneration in a Rodent Model

Early Stages of In Situ Bladder Regeneration in a Rodent Model

Characterization of the Early Proliferative Response of the Rodent Bladder to Subtotal Cystectomy: A Unique Model of Mammalian Organ Regeneration

In vitro evaluation of the bioactive factors preserved in porcine small intestinal submucosa through cellular biological approaches

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