Christopher Sherman

University of Toronto, Toronto, Ontario, Canada

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Publications (6)20.52 Total impact

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    ABSTRACT: Experimentally, porcine bladder acellular matrix (ACM) that mimics extracellular matrix has excellent potential as a bladder substitute. Herein we investigated the spatial localization and expression of different key cellular and extracellular proteins in the ACM; furthermore, we evaluated the inherent mechanical properties of the resultant ACM prior to implantation. Using a proprietary decellularization method, the DNA contents in both ACM and normal bladder were measured; in addition we used immunohistochemistry and western blots to quantify and localize the different cellular and extracellular components, and finally the mechanical testing was performed using a uniaxial mechanical testing machine. The mean DNA content in the ACM was significantly lower in the ACM compared to the bladder. Furthermore, the immunohistochemical and western blot analyses showed that collagen I and IV were preserved in the ACM, but possibly denatured collagen III in the ACM. Furthermore, elastin, laminin and fibronectin were mildly reduced in the ACM. Although the ACM did not exhibit nucleated cells, residual cellular components (actin, myosin, vimentin and others) were still present. There was, on the other hand, no significant difference in the mean stiffness between the ACM and the bladder. Although our decellularization method is effective in removing nuclear material from the bladder while maintaining its inherent mechanical properties, further work is mandatory to determine whether these residual DNA and cellular remnants would lead to any immune reaction, or if the mechanical properties of the ACM are preserved upon implantation and cellularization.
    Biomedical Materials 06/2008; 3(2):025015. DOI:10.1088/1748-6041/3/2/025015 · 3.70 Impact Factor
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    ABSTRACT: Tissue engineered organs require an immediately perfused vascular tree. Currently, neovascularization assessment requires animal sacrifice and graft harvest. In this pilot study we assess whether neovascularization of an engineered urinary bladder construct is enhanced with vascular-derived endothelial growth factor (VEGF) and assessable non-invasively with dynamic contrast-enhanced MRI (DCE-MRI). Rabbit bladder acellular matrix was hybridized with hyaluronic acid (ACM-HA), fortified with one of three concentrations (0 ng, 10 ng, or 20 ng per gram of tissue) of vascular-derived endothelial growth factor (VEGF), and grafted onto bladders in nine rabbits (3 per VEGF concentration). At 1, 2 and 3 weeks, one rabbit from each VEGF group underwent DCE-MRI and graft harvest. Microvasculature was quantified with scrial optical transverse sectioning of CD31 stained whole mounts using PCl software. Masson trichrome and H&E staining were used to assess cellular proliferation and fibrosis. There was a significant difference in mean microvascular area (MVA) between the 10 and 20 ng VEGF groups (230187 vs 477894 microm2, P=0.014) but not between the 0 and 10 ng groups (210497 microm2, P=0.21). Gadolinium uptake increased with MVA and correlated with it on linear regression analysis (Pearson's correlation coefficient r=0.71). At three weeks, stromal cellularity was greatest, and fibrosis was least, in the high VEGF group. This preliminary work demonstrates improved neovascularization of bladder constructs with VEGF fortification of ACM-HA and the feasibility of MRI as a non-invasive method to assume angiogenesis in tissue engineered constructs.
    Journal of Biomedical Materials Research Part A 05/2006; 77(2):390-5. DOI:10.1002/jbm.a.30648 · 3.37 Impact Factor
  • Walid A Farhat · Jun Chen · Christopher Sherman · Lisa Cartwright · Andre Bahoric · Herman Yeger ·
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    ABSTRACT: Urinary bladder tissue engineering utilizing autologous cell-seeded scaffolds requires enough bladder cells to populate a large surface area which may be difficult to obtain from abnormal bladders. We evaluated whether a fibrin glue spray technique enhances cell seeded acellular matrix (ACM) repopulation in a porcine bladder model. Porcine urothelial and smooth muscle cells cultured from open bladder biopsy were sprayed with or without fibrin glue onto porcine bladder ACM. After 10 days in vitro, constructs were implanted onto porcine bladders (4/group) and harvested after 1 or 6 weeks for H&E and immunohistochemical staining. In vitro, fibrin glue was associated with more continuous cell growth and enhanced cellular organization, maintained particularly in the periphery in vivo, where both groups demonstrated central fibrosis. While fibrin glue enhanced cellular organization on ACM in vitro, central fibrosis in vivo suggests that factors supporting seeded cell survival are lacking.
    The Canadian Journal of Urology 04/2006; 13(2):3000-8. · 0.98 Impact Factor
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    ABSTRACT: To compare the diagnostic imaging findings with the histological lesions in upper pole nephrectomy (UPN) specimens of duplex system ureteroceles, using renal ultrasonography (US) and nuclear renal scintigraphy. Between 1992 and 2000, 86 patients with a ureterocele in a duplex system underwent surgery. The results from US were reviewed in 84 patients by a radiologist, for echogenicity, parenchymal thinning and hydronephrosis; 77 nuclear renal scans describing the differential function of the upper poles were also reviewed. Fifty-five patients underwent UPN (25 antenatal, 30 postnatal; 18 intravesical, 37 extravesical) and the specimens were available for independent review by a pathologist, describing five histological categories, i.e. chronic interstitial inflammation, fibrosis, tubular atrophy, glomerulosclerosis and dysplasia. Histological lesions were categorized as severe (> 25%) or minimal (<or= 25%). Radiological features and the histology of UPN were then analysed, and correlated using Fisher's exact test and multivariate analysis. Severe histological lesions were reported in 38 specimens (69%) and minimal lesions in 17 UPN specimens (31%). Severe parenchymal thinning was associated with a severe pathological lesion (P < 0.02). There was no correlation with the echogenicity or degree of hydronephrosis. Dysplasia, found in 64% of specimens, did not correlate with increased echogenicity. Minimally functioning upper poles on nuclear renal scan (<or= 4% overall function) were significantly associated with severe histological lesions (P = 0.01). There was no correlation between diagnostic imaging features and the mode of presentation or type of ureterocele. Multivariate analysis, severe parenchymal thinning on renal US and minimal function on nuclear renal scan can be used to predict the severity of histological lesions of the upper pole. These results may be helpful in the making therapeutic decisions for patients with ureteroceles in duplex systems.
    BJU International 05/2003; 91(7):678-82. DOI:10.1046/j.1464-410X.2003.04247.x · 3.53 Impact Factor
  • Walid Farhat · Jeffrey Traubici · Christopher Sherman · Tara Williams · Paul Babyn · Gordon McLorie ·
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    ABSTRACT: Contrast medium enhanced harmonic ultrasound is a recently developed ultrasound technique that improves the assessment of renal parenchymal vascularity. We performed a preliminary study to define the ability of contrast enhanced ultrasound with harmonic imaging to detect and localize renal scars in a porcine model of experimentally induced pyelonephritis. Vesicoureteral reflux was surgically induced in 10 pigs weighing 10 kg. with the contralateral kidney serving as a control. Approximately 4 weeks after the creation of vesicoureteral reflux cystography confirmed reflux. Infection was induced by placing a suspension of paraffin broth impregnated with Escherichia coli in the bladder of each pig. At 4 to 8 weeks (mean 6.5) after the induction of infection a radiologist blinded to the side of the previous procedure performed conventional gray scale ultrasound, color Doppler ultrasound and contrast enhanced ultrasound with harmonic power imaging. The animals were sacrificed; the kidneys were inspected and tissues from the upper, mid and lower poles were sent for culture and histological examination. Histology results were compared with the findings of the 3 ultrasound modalities. All 10 pigs survived the surgical procedures with no complications. Post-contrast harmonic ultrasound images were available in 9 pigs (18 renal units). Harmonic ultrasound revealed decreased blood flow in 11 renal units, including the upper pole in 7, lower pole in 3, and upper and lower poles in 2. Renal tissue cultures were positive in 11 renal units (6 refluxing units). Histological findings revealed fibrosis in 10 renal units (8 refluxing units). Harmonic ultrasound findings in these 10 renal units showed 9 with changes consistent with inflammation or scars. Using histological results as the gold standard for renal injury harmonic ultrasound was more sensitive than gray scale ultrasound for detecting renal injury with 90% sensitivity, 75% specificity, 81% positive predictive value and 85% negative predictive value. Preliminary results indicate that contrast enhanced ultrasound with harmonic imaging is a sensitive method for determining renal scarring without the need for radiation exposure. It may be prove to be a useful adjunct for evaluating children who present with urinary tract infection.
    The Journal of Urology 10/2002; 168(3):1114-7. DOI:10.1097/01.ju.0000025869.03295.79 · 4.47 Impact Factor
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    ABSTRACT: We determined whether the histology of upper pole nephrectomy specimens vary with prenatal detection or ureterocele position. Between 1992 and 2000, 95 patients with ureteroceles associated with a duplex system underwent surgical interventions, including upper pole nephrectomy in 60. A total of 55 specimens, of which 25 and 30 involved a prenatal and postnatal diagnosis, and 18 and 37 involved an intravesical and extravesical location, respectively, were available for independent review by a single pathologist. Histological lesions were classified into the 5 categories of chronic interstitial inflammation, fibrosis, tubular atrophy, glomerulosclerosis and dysplasia. Each category was divided into moderate/severe histological lesions (greater than 25% involvement) and minimal/mild lesions (25% or less involvement). A moderate/severe histological lesion was identified in 38 patients (69%) and a minimal/mild lesion was detected in 17 (31%), while dysplasia was present in 35 (64%). There was no significant difference in histological lesions and mode of presentation. In contrast to intravesical ureteroceles, extravesical ureteroceles were associated with severe fibrosis and tubular atrophy (p <0.05). Chronic interstitial inflammation, fibrosis, tubular atrophy and glomerulosclerosis in each specimen were graded moderate/severe (greater than 25% involved) in 55%, 67%, 66% and 53%, respectively. Prenatally diagnosed ureteroceles were not associated with less severe upper pole histological lesions. We noted pathological differences when comparing specimens according to ureterocele position, but chronic inflammation and dysplasia were similar in intravesical and extravesical ureterocele cases. It appears that the histological lesions observed are not progressive or reversible. Therefore, the goals of clinical management should focus on providing adequate drainage, antibiotic prophylaxis coverage and followup of reflux rather than the preservation or enhancement of upper pole function.
    The Journal of Urology 09/2002; 168(3):1123-6. DOI:10.1097/01.ju.0000025866.15856.0f · 4.47 Impact Factor