Recombinant hepatocyte growth factor treatment in a canine model of congenital liver hypoplasia

Kruitwagen, Hedwig S.; Arends, Brigitte; Spee, Bart; Brinkhof, Bas; Ingh, T.S.G.A.M. van den; Rutten, Victor P.M.G.; Penning, Louis C.; Roskams, Tania; Rothuizen, J.

doi:10.1111/j.1478-3231.2011.02513.x

Cited by 13 publications

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References 40 publications

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“…13,24,31 Hepatic regeneration as evidenced by an increase in liver volume and return of biochemical parameters to normal occurs in many dogs following attenuation of a CPS, or administration of hepatocyte growth factor. 9,14,15,28,29 However, in some patients liver function never returns to normal, and portal hypertension results in development of multiple acquired shunts, 9,16,20,21 leading to speculation that the liver’s ability to respond to normal trophic factors is impaired.…”

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confidence: 99%

Evaluation of Hepatic Steatosis in Dogs With Congenital Portosystemic Shunts Using Oil Red O Staining

et al. 2013

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The aims of this prospective study were to quantify steatosis in dogs with congenital portosystemic shunts using a fat-specific stain, to compare the amount of steatosis in different lobes of the liver, and to evaluate intra- and inter-Observer variability in lipid point counting. Computer-assisted point counting of lipid droplets was undertaken following Oil-Red-O staining in 21 dogs with congenital portosystemic shunts and 9 control dogs. Dogs with congenital portosystemic shunts had significantly more small lipid droplets (< 6 μ) than control dogs (p = 0.0013 and 0.0002, respectively). There was no significant difference in steatosis between liver lobes for either control dogs and CPS dogs. Significant differences were seen between observers for the number of large lipid droplets (> 9 μ) and lipogranulomas per tissue point (p = 0.023 and 0.01, respectively). In conclusion, computer-assisted counting of lipid droplets following Oil Red O staining of liver biopsy samples allows objective measurement and detection of significant differences between dogs with CPS and normal dogs. This method will allow future evaluation of the relationship between different presentations of CPS (anatomy, age, breed) and lipidosis, as well as the impact of hepatic lipidosis on outcomes following surgical shunt attenuation.

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Section: Introductionmentioning

confidence: 99%

Evaluation of Hepatic Steatosis in Dogs With Congenital Portosystemic Shunts Using Oil Red O Staining

et al. 2013

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“…Companion animal models also may help researchers to understand liver diseases including those associated with copper overload, drug-induced injury, and regeneration 6 . For example, congenital portosystemic shunts with associated liver atrophy are common in dogs, and published and ongoing studies aimed at enhancing regeneration may identify agents that could be useful in human beings 7, 8…”

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confidence: 99%

One What? Why GI Researchers Should Know and Care About the One Health Initiative

Wells

2016

Cellular and Molecular Gastroenterology and Hepatology

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“…,2 R Liberal,* 2 C Grant, 2 C Grant, 2 G Mieli-Vergani, 2 D Vergani, 2 M Longhi 1. Faculdade de Medicina da Universidade do Porto, Porto, Portugal; 2 King's College London, London, UK…”

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PMO-135 Zinc finger e-box binding homeobox 1 (ZEB1) induces epithelial to mesenchymal transition (EMT) and promotes tumour progression in hepatocellular carcinoma (HCC): Abstract PMO-135 Figure 1

Sreekumar

Mirnezami

Wilson

et al. 2012

Gut

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Introduction There has been increasing interest in the possibility of using spontaneous canine hepatic disease as a model for those in human beings.1 Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of the liver and intrahepatic portal veins. While the condition is extremely rare in people, it is more common in dogs. Surgical CPSS attenuation results in liver growth and development of the intrahepatic portal vasculature, associated with clinical improvement. 2 The precise mechanism of this hepatic response is unknown; we hypothesised that it is due to hepatic regeneration and angiogenesis. The study aimed to measure the mRNA expression of growth factors and receptors involved in liver regeneration and angiogenesis in liver biopsies from dogs with CPSS before and after partial attenuation. Methods Dogs treated for CPSS were prospectively recruited to the study and liver biopsy samples were collected and placed in RNAlater. The expression of nine genes related to liver regeneration and angiogenesis were evaluated using quantitative polymerase chain reaction (qPCR). Differences in gene expression were assessed using independent or paired T tests. Significance was set at the 5% level (p¼0.05). Results Liver biopsies were collected from 49 CPSS dogs to seven control dogs. 24 dogs tolerated complete attenuation of their CPSS and 25 tolerated partial attenuation. A second surgery was performed in all partial attenuation dogs to achieve complete attenuation and a follow-up biopsy was taken. HGF mRNA expression was significantly decreased in CPSS dogs compared with controls. There were significant increases in mRNA expression of HGF, MAT2a andVEGFR2 following partial CPSS attenuation. In addition, dogs that could tolerate complete attenuation had significantly greater MAT2a, VEGFR2 and TGFbR2 mRNA expression. Conclusion The results of this study indicate that the liver regeneration and angiogenesis are involved in the hepatic response to surgery in dogs with CPSS. This suggests that canine CPSS could be a useful, naturally occurring model of liver regeneration.Competing interests None declared. Introduction Cellular transplantation is an alternative to liver transplantation, however provision of primary human hepatocytes is limited. Human embryonic stem cell-derived hepatocyte-like cells (ES-HLCs) represent a renewable source of functional hepatocytes. However, engraftment levels of these cells in the liver is low. The mechanisms regulating interactions between transplanted hepatocytes and the host liver remain unclear. Elucidation of these mechanisms may provide a means to enhance recruitment and engraftment in vivo. Methods ES-HLCs were generated using our previously published protocol.1 Functionality of cells was demonstrated biochemically and by transplantation into immunocompromised fumaryl acetoacetate hydrolase knock-out (FAH À/À ) mice. Microarray analysis of adhesion molecule expression was undertaken and compared with primary human hepatocytes. Adhesion molecule expression of ESHLCs was assesse...

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Recombinant hepatocyte growth factor treatment in a canine model of congenital liver hypoplasia

Abstract: Transient in vivo liver growth is shown using CPPS as a naturally occurring large animal model, indicating the therapeutic potential of HGF in liver disease.

Cited by 13 publications

References 40 publications

Evaluation of Hepatic Steatosis in Dogs With Congenital Portosystemic Shunts Using Oil Red O Staining

Evaluation of Hepatic Steatosis in Dogs With Congenital Portosystemic Shunts Using Oil Red O Staining

One What? Why GI Researchers Should Know and Care About the One Health Initiative

PMO-135 Zinc finger e-box binding homeobox 1 (ZEB1) induces epithelial to mesenchymal transition (EMT) and promotes tumour progression in hepatocellular carcinoma (HCC): Abstract PMO-135 Figure 1

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