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| 1 | Dynamic tracking of stem cells in an acute liver failure model显示文摘AIM:To investigate a dual labeling technique,which would enable real-time monitoring of transplanted embryonic stem cell(ESC) kinetics,as well as long-term tracking.METHODS:Liver damage was induced in C57/BL6 male mice(n = 40) by acetaminophen(APAP) 300 mg/kg administered intraperitoneally.Green fluorescence protein(GFP) positive C57/BL6 mouse ESCs were stained with the near-infrared fluorescent lipophilic tracer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide(DiR) immediately before transplantationinto the spleen.Each of the animals in the cell therapy group(n = 20) received 5 × 10 6 ESCs 4 h following treatment with APAP.The control group(n = 20) received the vehicle only.The distribution and dynamics of the cells were monitored in real-time with the IVIS Lumina-2 at 30 min post transplantation,then at 3,12,24,48 and 72 h,and after one and 2 wk.Immunohistochemical examination of liver tissue was used to identify expression of GFP and albumin.Plasma alanine aminotransferase(ALT) was measured as an indication of liver damage.RESULTS:DiR-stained ESCs were easily tracked with the IVIS using the indocyanine green filter due to its high background passband with minimal background autofluorescence.The transplanted cells were confined inside the spleen at 30 min post-transplantation,gradually moved into the splenic vein,and were detectable in parts of the liver at the 3 h time-point.Within 24 h of transplantation,homing of almost 90% of cells was confirmed in the liver.On day three,however,the DiR signal started to fade out,and ex vivo IVIS imaging of different organs allowed signal detection at time-points when the signal could not be detected by in vivo imaging,and confirmed that the highest photon emission was in the liver(P < 0.0001).At 2 wk,the DiRsignal was no longer detectable in vivo ;however,immunohistochemistry analysis of constitutively-expressed GFP was used to provide an insight into the distribution of the cells.GFP +ve cells were detected in tissue sections resembling hepatocytes and were dispersed throughout the hepatic parenchyma,with the presence of a larger number of GFP +ve cells incorporated within the sinusoidal endothelial lining.Very faint albumin expression was detected in the transplanted GFP +ve cells at 72 h;however at 2 wk,few cells that were positive for GFP were also strongly positive for albumin.There was a significant improvement in serum levels of ALT,albumin and bilirubin in both groups at 2 wk when compared with the 72 h time-point.In the cell therapy group,serum ALT was significantly(P = 0.016) lower and albumin(P = 0.009) was significantly higher when compared with the control group at the 2 wk time-point;however there was no difference in mortality between the two groups.CONCLUSION:Dual labeling is an easy to use and cheap method for longitudinal monitoring of distribution,survival and engraftment of transplanted cells,and could be used for cell therapy models. | Tarek Ezzat Dipok Kumar Dhar Massimo Malago Steven WM Olde Damink | 2012 | World Journal of Gastroenterology2012，18，6： | 12 |
| 2 | Cholangiocarcinoma, gone without the Wnt?显示文摘Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy. | Anne T R Noll Thorsten Cramer Steven W M Olde Damink Frank G Schaap | 2016 | World Journal of Hepatology2016，8，26： | 3 |
| 3 | The gut-liver axis显示文摘 | Ruben G.J. Visschers Misha D. Luyer Frank G. Schaap Steven W.M. Olde Damink Peter B. Soeters | 2013 | Current Opinion in Clinical Nutrition and Metabolic Care2013，，5： | 2 |
| 4 | In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide显示文摘 | L.H.H.Olde Damink P.J. Dijkstra M.J.A. van Luyn P.B. van Wachem P. Nieuwenhuis J. Feijen | 1996 | Biomaterials1996，，7： | 2 |
| 5 | Glutaraldehyde as a crosslinking agent for collagen-based biomaterials 显示文摘 | Damink L H H O Dijkstra P J Van Luyn M J | 1995 | Journal of Materials Science: Materials in Medicine1995，8，6： | 1 |
| 6 | Moderate hypothermia prevents cerebral hyperemia and increase in intracranial pressure in patients undergoing liver transplantation for acute liver failure显示文摘 | Jalan R Damink SW Deutz NE | | 0，，12： | 1 |
| 7 | Role of ammonia and inflammation in minimal hepatic encephalopathy显示文摘 | Shawcross DL Wright G Olde Damink SW | 2007 | Metab Brain Dis2007，22，1： | 1 |
| 8 | Interorgan ammonia trafficking in liver disease显示文摘 | Steven W. M. Olde Damink Rajiv Jalan Cornelius H. C. Dejong | 2009 | Metabolic Brain Disease2009，，1： | 1 |
| 9 | Interorgan ammonia metabolism in liver failure:the basis of current and future therapies显示文摘 | Wright G Noiret L Olde Damink SW | | 0，，02： | 1 |
| 10 | Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment 显示文摘 | van den Broek MA Olde Damink SW Dejiong CH | 2008 | Liver Int2008，28，6： | 1 |
| 11 | Occurrence and formation of biologically active amines in foods 显示文摘 | ten Brink B Damink C Joosten H M L J | 1990 | International Journal of Food Microbiology1990，11，1： | 1 |
| 12 | Brain cytokine flux in acute liver failure and its relationship with intracranial hypertension显示文摘 | Gavin Wright Debbie Shawcross Steven W. M. Olde Damink Rajiv Jalan | 2007 | Metabolic Brain Disease (-)2007，，3： | 1 |
| 13 | Role of ammonia and inflammation in minimal hepatic encephalo pathy 显示文摘 | Shawcross DL Wright G Olde Damink SW | 2007 | Metab Brain Dis2007，22，1： | 1 |
| 14 | Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow显示文摘 | Rajiv Jalan Steven W.M. Olde Damink Peter C. Hayes Nicolaas E.P. Deutz Alistair Lee | 2004 | Journal of Hepatology2004，，4： | 1 |
| 15 | Re-view article : pancreatic renin-angiotensin systems inhealth and disease显示文摘 | Skipworth JR Szabadkai G Olde Damink SW | 2011 | Aliment Pharmacol Ther2011，34，8： | 1 |
| 16 | Role of ammonia and inflammation in minimal hepatic encephaIopathy 显示文摘 | Shawcross DL Wright G Olde Damink SW | 2007 | Metab Brain Dis2007，22，1： | 1 |
| 17 | Brain cytokine flux in acute liver failure and its relation-ship with intracranial hypertension显示文摘 | Wright G Shawcross D Olde Damink SW | 2007 | Metab Brain Dis2007，22，34： | 1 |
| 18 | Liver failure after partial hepatic resection : definition, pathophysiology, risk factors and treatment显示文摘 | Van den Brock MA Olde Damink SW Dejong CH | 2008 | Liver Int2008，28，： | 1 |
| 19 | Pulmonary and Blood Stream Infections in Adult Living Donor and Cadaveric Liver Transplant Patients显示文摘 | Fuat H. Saner Steven W. M. Olde Damink Goran Pavlakovic Maartje A. J. van den Broek Peter-Michael Rath Georgios C. Sotiropoulos Arnold Radtke Ali Canbay Andreas Paul Silvio Nadalin Massimo Malagó Christoph E. Broelsch | 2008 | Transplantation2008，，11： | 1 |
| 20 | Moderate hypothernfia in patients with acute liver failure and uncon- trolled intracranial hypertension 显示文摘 | Jalan R Olde Damink SW Deutz NE | 2004 | Gastroenterology2004，127，5： | 1 |
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