Role of Basic Fibroblast Growth Factor in the Neuropathic Bladder Phenotype

Beqaj, Safedin; Donovan, Jena L.; Liu, Dennis B.; Harrington, Daniel A.; Alpert, Seth A.; Cheng, Earl Y.

doi:10.1097/01.ju.0000176633.92150.4e

Cited by 26 publications

(24 citation statements)

References 18 publications

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“…Furthermore, bFGF causes a significant decrease in elastin mRNA expression in aortic SMC (Carreras et al, 2002). Consistent with the Beqaj et al (2005) also reported increased bFGF expression in cultured SMCs derived from neuropathic bladder, and bFGF has strong mitogenic effects on cultured bladder SMCs. Therefore, bFGF effects may be a component in the development of neuropathic bladder abnormality.…”

Section: Discussionsupporting

confidence: 72%

Differentially expressed gene networks in cultured smooth muscle cells from normal and neuropathic bladder

Dozmorov

Kropp

Hurst

et al. 2007

J. Smooth Muscle Res.

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Neuropathic bladder dysfunction results from abnormal development of the spine, spinal cord injuries, or diseases such as diabetics. Patients with neuropathic bladders often require surgical intervention such as bladder reconstruction to improve incontinence and prevent renal damage. Tissue engineering with ex-vivo cultured bladder cells has been suggested as one means for improving bladder function. However, we previously demonstrated that cultured bladder smooth muscle cells (SMCs) derived from neuropathic bladder exhibit and maintain altered pathologic phenotypes in culture. To identify genes that are responsible for the abnormal neuropathic phenotypes specifically elevated cell proliferation, the expression levels of 1,185 genes were compared between cultured SMCs derived from normal and neuropathic bladders using a cDNA array consisting of well-annotated genes. The expression data were analyzed using several methods to identify differentially expressed genes. The resulting sets of differentially expressed genes were examined by pathway analysis to identify the networks that remain abnormal in the culture-stable phenotype of neuopathic SMCs. A total of 18 genes that are differentially expressed between cultured normal and neuropathic bladder SMCs were identified. Of these 17 were up-regulated greater than 2-fold in neuropathic bladder SMCs, six of them along with one gene that was not upregulated greater than 2-fold in cultured neuropathic bladder SMCs were confirmed and identified by more stringent analysis methods including significance analysis of microarrays, class comparison, and class prediction analyses. The major dysregulated pathways include fibroblast growth factor signaling, PTEN signaling, and integrin signaling. Our results further suggest that altered neuropathic bladder SMC phenotypes is stable in the culture environments and that SMCs derived from diseased bladders may not be appropriate for tissue engineering purpose without modification of pathologically altered genes expression.

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Section: Discussionsupporting

confidence: 72%

Differentially expressed gene networks in cultured smooth muscle cells from normal and neuropathic bladder

Dozmorov

Kropp

Hurst

et al. 2007

J. Smooth Muscle Res.

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“…Specimens were dehydrated through a series of graded ethanol exchanges followed by paraffin embedding according to established protocols [23]. Samples were sectioned at a 5 lm thickness using a RM2125 RT Microtome (Leica, Nannockburn, IL) onto glass slides and subjected to Masson's Trichrome (Sigma-Aldrich, St. Louis, MO) staining as previously described [9,24]. Tissue containing slides were deparaffinized by heating followed by treatment with xylenes, graded ethanol washes, and deionized water.…”

Section: Histological Tissue Stainingmentioning

confidence: 99%

A Nonhuman Primate Model for Urinary Bladder Regeneration Using Autologous Sources of Bone Marrow-Derived Mesenchymal Stem Cells

et al. 2011

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Animal models that have been used to examine the regenerative capacity of cell-seeded scaffolds in a urinary bladder augmentation model have ultimately translated poorly in the clinical setting. This may be due to a number of factors including cell types used for regeneration and anatomical/ physiological differences between lower primate species and their human counterparts. We postulated that mesenchymal stem cells (MSCs) could provide a cell source for partial bladder regeneration in a newly described nonhuman primate bladder (baboon) augmentation model. Cell-sorted2 baboon MSCs transduced with green fluorescent protein (GFP) were seeded onto small intestinal submucosa (SIS) scaffolds. Baboons underwent an approximate 40%-50% cystectomy followed by augmentation cystoplasty with the aforementioned scaffolds or controls and finally enveloped with omentum. Bladders from sham, unseeded SIS, and MSC/SIS scaffolds were subjected to trichrome, H&E, and immunofluorescent staining 10 weeks postaugmentation. Immunofluorescence staining for muscle markers combined with an anti-GFP antibody revealed that >90% of the cells were GFP Disclosure of potential conflicts of interest is found at the end of this article.

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“…The opposite face of the scaffold could them be modified using a second component, which in this case was a mixture of PGA and urothelial cells, since these cells could potentially send necessary signals to smooth muscle cells during regeneration. (Beqaj, 2005;Imamura, 2007) When the human bladder smooth muscle cells and urothelial cells where embedded in a PA-scaffold with a growth factor (bFGF) and incubated in vivo in a subcutaneous nude rat model, it was found that the human bladder smooth muscle cells were retained and composed the majority of the scaffold cellular content. It was also found that the system which uses a combination of PGA, PA, growth factors and cells demonstrated higher levels of phenotypic alpha-smooth muscle actin than control scaffolds made of PGA and cells only.…”

Section: Bioactive Peptides and Peptide Amphiphiles For Regeneration mentioning

confidence: 99%

“…Characterization of bladder smooth muscle cells derived from patients with myelomeningocele indicates that cultured bladder smooth muscle cells possess different characteristics than their normal counterparts. (Lin, 2004;Beqaj, 2005) Finally, the aforementioned augmented bladders continued to be non-contractile thus requiring the patients to presumably self catheterize for the remainder of their lifespan. Although groundbreaking in nature, much work needs to be performed in order to fully realize the goal of creating a functional bladder.…”

Section: The Urinary Bladdermentioning

confidence: 99%

Aspects of Urological Tissue Engineering

Sharma¹,

Rożkiewicz²

2011

Tissue Engineering for Tissue and Organ Regeneration

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Role of Basic Fibroblast Growth Factor in the Neuropathic Bladder Phenotype

Abstract: These novel findings support the hypothesis that bFGF is over expressed in the neuropathic bladder and directly influences an increase in SMC proliferation.

Cited by 26 publications

References 18 publications

Differentially expressed gene networks in cultured smooth muscle cells from normal and neuropathic bladder

Differentially expressed gene networks in cultured smooth muscle cells from normal and neuropathic bladder

A Nonhuman Primate Model for Urinary Bladder Regeneration Using Autologous Sources of Bone Marrow-Derived Mesenchymal Stem Cells

Aspects of Urological Tissue Engineering

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