检索结果-南通市图书馆

Hepatocyte cryopreservation:Is it time to change the strategy?

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2010年第1期16卷 1-14页

作者： Xavier Stéphenne mustapha najimi Etienne M Sokal Catholic University of Louvain and St Luc Clinics Paediatric Department(HPED)PEDI unitLaboratory of Paediatric Hepatology and Cell Therapy

Liver cell transplantation presents clinical benefit in patients with inborn errors of metabolism as an alternative,or at least as a bridge,to orthotopic liver transplantation.The success of such a therapeutic approach remains limited by the quality of the transplanted cells.Cryopreservation remains the best option for long-term storage of hepatocytes,providing a permanent and sufficient cell supply.However, isolated adult hepatocytes are poorly resistant to such a process,with a significant alteration both at the morphological and functional levels.Hence,the aim of the current review is to discuss the state of the art regarding widely-used hepatocyte cryopreservation protocols,as well as the assays performed to analyse the post-thawing cell quality both in vitro and in vivo. The majority of studies agree upon the poor quality and efficiency of cryopreserved/thawed hepatocytes as compared to freshly isolated hepatocytes.Intracellular ice formation or exposure to hyperosmotic solutionsremains the main phenomenon of cryopreservation process,and its effects on cell quality and cell death induction will be discussed.The increased knowledge and understanding of the cryopreservation process will lead to research strategies to improve the viability and the quality of the cell suspensions after thawing.Such strategies,such as vitrification,will be discussed with respect to their potential to significantly improve the quality of cell suspensions dedicated to liver cell-based therapies.

关键词： Hepatocyte Cryopreservation Quality Mitochondria Intracellular ice formation

Hepato-biliary profile of potential candidate liver progenitor cells from healthy rat liver

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2012年第27期18卷 3511-3519页

作者： Cédric Maerckx Isabelle Scheers Tatiana Tondreau David Campard Omar Nyabi mustapha najimi Etienne Sokal Laboratory of Pediatric Hepatology and Cell Therapy Université Catholique de Louvain1200 BrusselsBelgium

AIM:To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent advanced hepatogenic profile as that obtained in humans.METHODS:Rat fibroblastic-like liver derived cells (rFLDC) were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry,immunocytochemistry,reverse transcription polymerase chain reaction and functional assays.RESULTS:rFLDC exhibit fibroblastoid morphology,express mesenchymal (CD73,CD90,vimentin,-smooth muscle actin),hepatocyte (UGT1A1,CK8) and biliary (CK19) markers.Moreover,these cells are able to store glycogen,and have glucose 6 phosphatase activity,but not UGT1A1 activity.Under the hepatogenic differentiation protocol,rFLDC display an up-regulation of hepatocyte markers expression (albumin,tryptophan 2,3-dioxygenase,G6Pase) correlated to a down-regulation of the expression of the biliary marker CK19.CONCLUSION:Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC.However,we demonstrated the presence of an original rodent hepato-biliary cell type.

关键词：大鼠肝脏肝干细胞档案健康逆转录聚合酶链反应磷酸酶活性免疫细胞化学成纤维细胞

Silibinin induces hepatic stellate cell cycle arrest via enhancing p53/p27 and inhibiting Akt downstream signaling protein expression

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Hepatobiliary & Pancreatic Diseases International 2017年第1期16卷 80-87页

作者： Devaraj Ezhilarasan Jonathan Evraerts Brice Sid Pedro Buc Calderon Sivanesan Karthikeyan Etienne Sokal mustapha najimi institut de recherche expérimentale et clinique (irec) laboratory of pediatric hepatology and cell therapyuniversité catholique de louvain 1200 Brussels Belgium louvain drug research institute toxicology and cancer biology research group pmnt unituniversité catholique de louvain 1200 Brussels Belgium facultad de ciencias de la salud universidad arturo prat Iquique Chil department of pharmacology and environmental toxicology food and hepatotoxicology laboratory dr. alm post graduate institute of basic medical sciences university of madrastaramani campus Chennai-600 l13 India

BACKGROUND： Proliferation of hepatic stellate cells （HSCs） plays a pivotal role in the progression of liver fibrosis conse- quent to chronic liver injury. Silibinin, a flavonoid compound, has been shown to possess anti-fibrogenic effects in animal models of liver fibrosis. This was attributed to an inhibition of cell proliferation of activated HSCs. The present study was to gain insight into the molecular pathways involved in silibinin anti-fibrogenic effect. METHODS： The study was conducted on LX-2 human stellate cells treated with three concentrations of silibinin （10, 50 and 100 μmol/L） for 24 and 96 hours. At the end of the treatment cell viability and proliferation were evaluated. Protein expression of p27, p21, p53, Akt and phosphorylated-Akt was evaluated by Western blotting analysis and Ki-67 protein expression was by immunocytochemistry. Sirtuin activity was evaluated by chemiluminescence based assay. RESULTS： Silibinin inhibits LX-2 cell proliferation in doseand time-dependent manner; we showed that silibinin upregulated the protein expressions of p27 and p53. Such regulation was correlated to an inhibition of both downstream Akt and phosphorylated-Akt protein signaling and Ki-67 protein expression. Sirtuin activity also was correlated to silibinin- inhibited proliferation of LX-2 cells. CONCLUSION： The anti-proliferative effect of silibinin on LX-2 human steUate cells is via the inhibition of the expres- sions of various cell cycle targets including p27, Akt and sir- tuin signaling.

关键词： silibinin hepatic stellate cells in vitro cell cycle arrest proliferation

Cytokinome of adult-derived human liver stem/progenitor cells:immunological and inflammatory features

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Hepatobiliary Surgery and Nutrition 2018年第5期7卷 331-344页

作者： Mehdi Najar Emerence Crompot Gordana Raicevic Etienne M.Sokal mustapha najimi Laurence Lagneaux Laboratory of Clinical Cell Therapy Jules Bordet InstituteUniversitéLibre de Bruxelles(ULB)Campus ErasmeBatiment de Transfusion(Level+1)Brussels 1070Belgium Laboratory of Pediatric Hepatology and Cell Therapy Institute of Experimental&Clinical ResearchUniversitéCatholique de LouvainBrusselsBelgium

Background: Being non-immunogenic and capable of achieving major metabolic liver functions, adult-derived human liver stem/progenitor cells (ADHLSCs) are of special interest in the field of liver cell therapy. The cytokine repertoire of engrafted cells may have critical impacts on the immune response balance, particularly during cell transplantation. Methods: In this work, we analyzed the cytokinome of ADHLSCs during hepatogenic differentiation (HD) following stimulation with a mixture of inflammatory cytokines (I) in vitro and compared it to that of mature hepatocytes. Results: Independent of their hepatic state, ADHLSCs showed no constitutive expression of pro-inflammatory cytokines, which were significantly induced by inflammation (IL-1β, IL-6, IL-8, TNFα, CCL5, IL-12a, IL-12b, IL-23p19, IL-27p28 and EBI-3). IL1-RA and IDO-1, as immunoregulatory cytokines, were highly induced in undifferentiated ADHLSCs, whereas TGF-β was downregulated by both hepatic and inflammatory events. Interestingly, TDO-1 was exclusively expressed in ADHLSCs after hepatic differentiation and enhanced by inflammatory cytokines. Compared to mature hepatocytes, hepatic-differentiated ADHLSCs showed significantly different cytokine expression patterns. Conclusions: By establishing the cytokinome of ADHLSCs and highlighting their immunological and inflammatory features, we can enhance our knowledge about the safety and efficiency of the transplantation strategy.

关键词： Immunology adult-derived human liver stem/progenitor cells (ADHLSCs) mesenchymal cells cytokinome gene expression analysis

Epithelial cells with hepatobiliary phenotype:Is it another stem cell candidate for healthy adult human liver?

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2007年第10期13卷 1554-1560页

作者： Dung Ngoc Khuu mustapha najimi Etienne M Sokal Université Catholique de Louvain Laboratory of Pediatric Hepatology & Cell therapyBrusselsBelgium

AIM:To investigate the presence and role of liver epithelial cells in the healthy human adult liver.METHODS:Fifteen days after human hepatocyte primary culture,epithelial like cells emerged and started proliferating.Cell colonies were isolated and sub-cultured for more than 160 d under specific culture conditions.Cells were analyzed for each passage using immunofluorescence,flow cytometry and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS:Flow cytometry analysis demonstrated that liver epithelial cells expressed common markers for hepatic and stem cells such as CD90,CD44 and CD29 but were negative for CD34 and CD117.Using immunofluorescence we demonstrated that liver epithelial cells expressed not only immature(α-fetoprotein)but also differentiated hepatocyte(albumin and CK-18)and biliary markers(CK-7 and 19),whereas they were negative for OV-6.RT-PCR analysis confirmed immunofluorescence data and revealed that liver epithelial cells did not express mature hepatocyte markers such as CYP2B6,CYP3A4 and tyrosine amino-transferase.Purified liver epithelial cells were transplanted into SCID mice.One month after transplantation,albumin positive cell foci were detected in the recipient mouse parenchyma.CONCLUSION:According to their immature and bipotential phenotype,liver epithelial cells might represent a pool of precursors in the healthy human adult liver other than oval cells.

关键词：上皮细胞肝胆管表现型肝脏干细胞细胞分化细胞疗法

Stem cells for liver tissue repair:Current knowledge and perspectives

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2008年第6期14卷 864-875页

作者： Philippe A Lysy David Campard Fran oise Smets mustapha najimi Etienne M Sokal Université Catholique de Louvain & Cliniques Universitaires Saint Luc HPED Department Unit PEDI Laboratory of Pediatric Hepatology and Cell Therapy Brussels 1200 Belgium

Stem cells from extra-or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated. Therefore, they are being increasingly considered for future applications in liver cell therapy. In that field, liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation, while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures. However, the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype, both in vitro and in vivo. Furthermore, the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures. The present review focuses on the current knowledge of the stem cell potential for liver therapy. We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo. We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.

关键词：干细胞肝细胞细胞分化透视技术电流

Regulation of hepatic EAAT-2 glutamate transporter expression in human liver cholestasis

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2014年第6期20卷 1554-1564页

作者： mustapha najimi Xavier Stéphenne Christine Sempoux Etienne Sokal Université Catholique de Louvain Institut de Recherche Expérimentale et Clinique (IREC) Laboratory of Pediatric Hepatology and Cell Therapy Anatomo-pathology Cliniques Universitaires St-Luc Université Catholique de Louvain

AIM: To investigate the activity and expression of EAAT2 glutamate transporter in both in vitro and in vivo models of cholestasis. METHODS: This study was conducted on human hepatoblastoma HepG2 cell cultures, the liver of bile duct ligated rats and human specimens from cholestatic patients. EAAT2 glutamate transporter activity and expression were analyzed using a substrate uptake assay, immunofluorescence, reverse transcription-polymerase chain reaction, and immunohistochemistry, respectively. RESULTS: In HepG2 cells, cholestasis was mimicked by treating cells with the protein kinase C activator, phorbol 12-myristate 13-acetate. Under such conditions, EAAT2 transporter activity was decreased both at the level of substrate affinity and maximal transport velocity. The decreased uptake was correlated with intracellular translocation of EAAT2 molecules as demonstrated using immunofluorescence. In the liver of bile duct ligated rats, an increase in EAAT2 transporter protein expression in hepatocytes was demonstrated using immunohistochemistry. The same findings were observed in human liver specimens of cholestasis in which high levels of γ-glutamyl transpeptidase were documented in patients with biliary atresia and progressive familial intrahepatic cholestasis type 3. CONCLUSION: This study demonstrates the alteration in glutamate handling by hepatocytes in liver cholestasis and suggests a potential cross-talk between glutamatergic and bile systems.

关键词： Glutamate transport Hepatocyte Bile duct ligation

Use of mesenchymal stem cells to treat liver fibrosis:Current situation and future prospects

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2015年第3期21卷 742-758页

作者： Silvia Berardis Prenali Dwisthi Sattwika mustapha najimi Etienne Marc Sokal Laboratory of Pediatric Hepatology and Cell Therapy Institut de Recherche Expérimentale et CliniqueCliniques Universitaires St LucUniversité Catholique de Louvain1200 BrusselsBelgium

Progressive liver fibrosis is a major health issue for which no effective treatment is available,leading to cirrhosis and orthotopic liver transplantation.However,organ shortage is a reality.Hence,there is an urgent need to find alternative therapeutic strategies.Cellbased therapy using mesenchymal stem cells(MSCs) may represent an attractive therapeutic option,based ontheir immunomodulatory properties,their potential to differentiate into hepatocytes,allowing the replacement of damaged hepatocytes,their potential to promote residual hepatocytes regeneration and their capacity to inhibit hepatic stellate cell activation or induce their apoptosis,particularly via paracrine mechanisms.The current review will highlight recent findings regarding the input of MSC-based therapy for the treatment of liver fibrosis,from in vitro studies to pre-clinical and clinical trials.Several studies have shown the ability of MSCs to reduce liver fibrosis and improve liver function.However,despite these promising results,some limitations need to be considered.Future prospects will also be discussed in this review.

关键词： Liver fibrosis Cirrhosis Mesenchymal stem cells Ce

Plant derived antioxidants and antifibrotic drugs:past,present and future

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Coastal Life Medicine 2014年第9期2卷 738-745页

作者： Devaraj Ezhilarasan Etienne Sokal Sivanesan Karthikeyan mustapha najimi Institut de Recherche Expérimentale et Clinique Laboratory of Pediatric Hepatology and Cell TherapyUniversitéCatholique de LouvainBrusselsBelgium Department of Pharmacology and Environmental Toxicology Food and Hepatotoxicology LaboratoryDr.ALM Post Graduate Institute of Basic Medical SciencesUniversity of MadrasChennaiIndia

Hepatic fibrosis occurs as a wound-healing process after several forms of chronic hepatic injury.Activation and proliferation of hepatic stellate cells play pivotal role in the pathogenesis of hepatic fibrosis.Many researchers,from the therapeutic perspective,have focused their attention on searching for novel agents with inhibitory effects on hepatic stellate cells proliferation and activation to prevent hepatic fibrogenesis and a number of plant derived antioxidants have been tested as anti-fibrogenic agents,they generally suppress proliferation and collagen synthesis.Plants remain an imperative source of novel drugs,novel drug leads and new chemical entities.The plant based drug discovery resulted primarily in the development of antioxidant,anti-cancer and other anti-infectious agents and continues to contribute to the new leads in clinical trials.This review summarizes some of those most important plant derived anti-fibrotic drugs and their beneficial effects on experimentally induced hepatic fibrosis in vitro and in vivo.The plant derived antioxidant compounds described herein are curcumin,silymarin,silibinin,baicalein,resveratrol,salvianolic acids,tetrandine,quercetin and berberine.Studies from ours and as demonstrated by pervious workers much information has been accumulated over the past two decades through in vivo and in vitro.In light of those studies,it has been confirmed that plants derived antioxidants,particularly flavanoids,show a significant influence to block hepatic fibrosis regardless of any etiology.This review outlines recent progress in the use of plant derived drugs against experimentally induced liver fibrosis by in vitro and in vivo studies and summarizes the possible mechanisms anti-fibrotic effects of these compounds.

关键词： Curcumin Hepatic stellate cells Hepatic fibrosis Antioxidant Silibinin