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| 1 | Hepatic fibrosis: It is time to go with hepatic stellate cell-specifictherapeutic targets显示文摘Hepatic fibrosis is a pathological lesion, characterized by the progressive accumulation of extracellular matrix(ECM) in the perisinusoidal space and it is a major problem in chronic liver diseases. Phenotypic activation of hepatic stellate cells(HSC) plays a central role in the progression of hepatic fibrosis. Retardation of proliferation and clearance of activated HSCs from the injured liver is an appropriate therapeutic strategy for the resolution and treatment of hepatic fibrosis. Clearance of activated HSCs from the injured liver by autophagy inhibitors, proapoptotic agents and senescence inducers with the high affinity toward the activated HSCs may be the novel therapeutic strategy for the treatment of hepatic fibrosis in the near future. | Devaraj Ezhilarasan Etienne Sokal Mustapha Najimi | 2018 | Hepatobiliary & Pancreatic Diseases International2018，17，3： | 56 |
| 2 | Stem cells for liver tissue repair:Current knowledge and perspectives显示文摘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. | Philippe A Lysy David Campard Fran oise Smets Mustapha Najimi Etienne M Sokal | 2008 | World Journal of Gastroenterology2008，14，6： | 22 |
| 3 | Use of mesenchymal stem cells to treat liver fibrosis:Current situation and future prospects显示文摘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. | Silvia Berardis Prenali Dwisthi Sattwika Mustapha Najimi Etienne Marc Sokal | 2015 | World Journal of Gastroenterology2015，21，3： | 22 |
| 4 | Liver cell transplantation for Crigler-Najjar syndrome type Ⅰ: Update and perspectives显示文摘Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term partial metabolic control of various diseases. Crigler-Najjar is the paradigm of such diseases in that the host liver is lacking one function with an otherwise normal parenchyma. The patient is at permanent risk for irreversible brain damage. The goal of liver cell transplantation is to reduce serum bilirubin levels within safe limits and to alleviate phototherapy requirements to improve quality of life. Preliminary data on Gunn rats, the rodent model of the disease, were encouraging and have led to successful clinical trials. Herein we report on two additional patients and describe the current limits of the technique in terms of durability of the response as compared to alternative therapeutic procedures. We discuss the future developments of the technique and new emerging perspectives. | Philippe A Lysy Mustapha Najimi Xavier Stéphenne Annick Bourgois Franoise Smets Etienne M Sokal | 2008 | World Journal of Gastroenterology2008，14，22： | 9 |
| 5 | Hepatocyte cryopreservation:Is it time to change the strategy?显示文摘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. | Xavier Stéphenne Mustapha Najimi Etienne M Sokal | 2010 | World Journal of Gastroenterology2010，16，1： | 9 |
| 6 | Silibinin induces hepatic stellate cell cycle arrest via enhancing p53/p27 and inhibiting Akt downstream signaling protein expression显示文摘BACKGROUND: Proliferation of hepatic stellate cells(HSCs) plays a pivotal role in the progression of liver fibrosis consequent 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 silibinininhibited proliferation of LX-2 cells. CONCLUSION: The anti-proliferative effect of silibinin on LX-2 human stellate cells is via the inhibition of the expressions of various cell cycle targets including p27, Akt and sirtuin signaling. | Devaraj Ezhilarasan Jonathan Evraerts Brice Sid Pedro Buc Calderon Sivanesan Karthikeyan Etienne Sokal Mustapha Najimi | 2017 | Hepatobiliary & Pancreatic Diseases International2017，16，1： | 7 |
| 7 | Epithelial cells with hepatobiliary phenotype:Is it another stem cell candidate for healthy adult human liver?显示文摘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. | Dung Ngoc Khuu Mustapha Najimi Etienne M Sokal | 2007 | World Journal of Gastroenterology2007，13，10： | 3 |
| 8 | Pertussis toxin-sensitive modulation of glutamate transport by endothelin-1 type A receptors in glioma cells显示文摘 | Mustapha Najimi Jean-Marie Maloteaux Emmanuel Hermans | 2004 | BBA - Biomembranes2004，，2： | 1 |
| 9 | Hepato-biliary profile of potential candidate liver progenitor cells from healthy rat liver显示文摘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. | Cédric Maerckx Isabelle Scheers Tatiana Tondreau David Campard Omar Nyabi Mustapha Najimi Etienne Sokal | 2012 | World Journal of Gastroenterology2012，18，27： | 1 |
| 10 | Sustained Engraftment and Tissue Enzyme Activity After Liver Cell Transplantation for Argininosuccinate Lyase Deficiency显示文摘 | Xavier Stéphenne Mustapha Najimi Catherine Sibille Marie–Cécile Nassogne Fran?oise Smets Etienne M. Sokal | 2006 | Gastroenterology2006，，4： | 1 |
| 11 | Native Umbilical Cord Matrix Stem Cells Express Hepatic Markers and Differentiate Into Hepatocyte-like Cells显示文摘 | David Campard Philippe A. Lysy Mustapha Najimi Etienne Marc Sokal | 2008 | Gastroenterology2008，，3： | 1 |
| 12 | Influence of inflammation on the immunological profile of adult derived human liver mesenchymal stem and stellate cells显示文摘 | Gordana Raicevic Mehdi Najar Mustapha Najimi Adil El Taghdouini Leo A. van Grunsven Etienne Sokal Michel Toungouz | 2014 | Cytotherapy2014，，： | 1 |
| 13 | Regulation of hepatic EAAT-2 glutamate transporter expression in human liver cholestasis显示文摘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. | Mustapha Najimi Xavier Stéphenne Christine Sempoux Etienne Sokal | 2014 | World Journal of Gastroenterology2014，20，6： | 0 |
| 14 | Human liver stem/progenitor cells decrease serum bilirubin in hyperbilirubinemic Gunn rat显示文摘AIM:To test the ability of adult-derived human liver stem/progenitor cells(ADHLSC)from large scale cultures to conjugate bilirubin in vitro and in bilirubin conjugation deficient rat.METHODS:ADHLSC from large scale cultures were tested for their phenotype and for their capacity to conjugate bilirubin in vitro after hepatogenic differentiation.In vivo,Gunn rats[uridine diphosphate-glucuronosyltransferase 1A1(UGT1A1)deficient animal]were injected with ADHLSC and cryopreserved hepatocytes(positive control).Two,4,13 and 27 wk posttransplantation,transplanted Gunn rat bilirubin serum levels were determined by high performance liquid chromatography.Human cell engraftment of trans-planted cells was assessed 27 wk post-transplantation using immunohistochemistry and RTqPCR.RESULTS:Large scale culture conditions do not modified ADHLSC phenotype,ADHLSC were able to specifically conjugate bilirubin.ADHLSC were intraportally injected into Gunn rats and blood UCB was measured at different times post-transplantation,infused-Gunn rats exhibited a metabolic effect 3 mo post-transplantation and maintained over a 6 mo period.ADHLSC engraftment into Gunn rat’s liver was demonstrated by RTqPCR and immunohistochemistry against albumin and UGT1A1.CONCLUSION:ADHLSC from large scale cultures are efficient in conjugating bilirubin in vitro and in restoring a deficient metabolic function(reducing bilirubin level)in hyperbilirubinemic rats. | Cédric Maerckx Tatiana Tondreau Silvia Berardis Jos van Pelt Mustapha Najimi Etienne Sokal | 2014 | World Journal of Gastroenterology2014，20，30： | 0 |
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