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 consider...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.展开更多
AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated...AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.展开更多
Hepatocellular carcinoma (HCC) is the commonest primary malignancy of the liver. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Orthotopic liver transplantation (OLT) ...Hepatocellular carcinoma (HCC) is the commonest primary malignancy of the liver. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Orthotopic liver transplantation (OLT) is a suitable therapeutic option for early,unresectable HCC particularly in the setting of chronic liver disease. Following on from disappointing initial results,the seminal study by Mazzaferro et al in 1996 established OLT as a viable treatment for HCC. In this study,the "Milan criteria" were applied achieving a 4-year survival rate similar to OLT for benign disease. Since then various groups have attempted to expand these criteria whilst maintaining long term survival rates. The technique of living donor liver transplantation has evolved over the past decade,particularly in Asia,and published outcome data is comparable to that of OLT. This article will review the evidence,indications,and the future direction of liver transplantation for liver cancer.展开更多
AIM: To investigate the capability of multidetector CT (MDCT) to diagnose HCC-associated arterioportal shunt (APS).METHODS: Two hundred and eighty-two patients with HCC received both thin-slice and enhancement MDCT sc...AIM: To investigate the capability of multidetector CT (MDCT) to diagnose HCC-associated arterioportal shunt (APS).METHODS: Two hundred and eighty-two patients with HCC received both thin-slice and enhancement MDCT scanning at early hepatic arterial phase, late hepatic arterial phase and portal venous phase, and digital subtract angiography (DSA) examination. Images were analyzed jointly by two experienced radiologists blinded to the opposite examination results, including the existence or not of APS, shunt locations, types and degrees of APS, with or without thrombosis. RESULTS: There were 56 APS associated with HCC, including 48 central, seven peripheral and one mixed, or 42 severe, seven moderate, seven mild APS. Fortyone severe, seven moderate and central APS were all revealed with MDCT and DSA. Seven mild and peripheral APS were all displayed with MDCT; only five of them displayed DSA, two faint shunt APS associated with massive HCC were missed. One mixed APS was demonstrated as severe combined with mild shunt with both MDCT and DSA.CONCLUSION: MDCT could diagnose not only DSA revealed APS, but also missed mild and peripheral APS with DSA due to faint shunt associated with massive HCC, is a simple, effective and noninvasive new technique for diagnosis of HCC-associated APS.展开更多
AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a no...AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a normal human liver cell line.METHODS： Net Ca^2＋ fluxes were measured with NMT, a technology that can obtain dynamic information of specific/selective ionic/molecular activities on material surfaces, non-invasively. The expression levels of TRPCl were increased by liposomal transfection, whose effectiveness was evaluated by Western-blotting and single cell reverse transcription-polymerase chain reaction.RESULTS： Ca^2＋ influxes could be elicited by adding 1 mmol/L CaCl2 to the test solution of HL-7702 cells. They were enhanced by addition of 20 μmol/L noradrenalin and inhibited by 100 μmol/L LaCl3 （a non-selective Ca^2＋ channel blocker）; 5 μmol/L nifedipine did not induce any change. Overexpression of TRPCl caused increased Ca^2＋ influx. Five micromoles per liter nifedipine did not inhibit this elevation, whereas 100 μmol/L LaCI3 did.CONCLUSION： In HL-7702 cells, there is a type of TRPCl-dependent Ca^2＋ channel, which could be detected v/a NMT and inhibited by La^3＋.展开更多
AIM： To detect the DNA binding activity of nuclear factor-kappaB （NF-KB） in rat hepatocyte and to investigate the effects of NF-KB on rat hepatocyte regeneration and apoptosis after 70% portal branch Iigation. METH...AIM： To detect the DNA binding activity of nuclear factor-kappaB （NF-KB） in rat hepatocyte and to investigate the effects of NF-KB on rat hepatocyte regeneration and apoptosis after 70% portal branch Iigation. METHODS： Sixty Wistar rats were randomly divided into control group and portal branch ligation group. The animals were killed 12 h, 1, 2, 3, 7, and 14 d after surgery to determine the contents of plasma ALT. Hepatocytes were isolated and nuclear protein was extracted. DNA binding activity of NF-KB was measured by ENSA. Hepatocyte regeneration and apoptosis were observed under microscope by TUNEL staining. The ultrastructural changes of liver were observed under electron microscope. RESULTS： Seventy percent portal branch ligation produced atrophy of the ligated lobes and the perfused lobes underwent compensatory regeneration, the total liver weight and plasma ALT levels were maintained at the level of sham-operated animals throughout the experiment. After 2 d of portal branch ligation, DNA binding activity of NF-KB in hepatocyte increased and reached its peak, the number of apoptotic hepatocyte in the ligated lobes and the number of mitotic hepatocyte in the perfused lobes also reached their peak. Typical apoptotic changes and evident fibrotic changes in the ligated lobes were observed under electron microscope. CONCLUSION： After 70% portal branch ligation, DNA binding activity of NF-KB in hepatocyte is significantly increased and NF-KB plays an important role in hepatocyte regeneration and apoptosis.展开更多
Objective： To investigate the relationship between the appearances of digital subtraction angiography （DSA） and the serum level of vascular endothelial growth factor （VEGF） in patients with primary hepatocellular...Objective： To investigate the relationship between the appearances of digital subtraction angiography （DSA） and the serum level of vascular endothelial growth factor （VEGF） in patients with primary hepatocellular carcinoma （HCC）. Methods： 24 HCC patients, 30 times DSA were examined, serum VEGF level was measured with the quantitative enzyme linked immunosorbent assay （ELISA） in patients and healthy control subjects in this study. Results： Among DSA for 24 patients with HCC, 18 of 24 cases showed hepatic artery blood supply of tumor. Four of 24 cases showed portal vein blood supply of tumor, 1 of 24 cases showed superior mesenteric artery blood supply of tumor and artery-venous shunt formation, and there was no blood supply to tumor in one case. Serum VEGF level in HCC[（χ＋s）194.5±14.2] ng/L was significant elevated to those in patients comparing with those of the normal controls （132.4±47.9） ng/L and marked differences （P〈0.01）. Conclusion： During the cases for plenty blood supply or arteryvenous shunt formation in patients with HCC, serum VEGF level markedly elevated in the patients of HCC. VEGF expression was significantly related to intrahepatic dissemination, recurrence and metastasis in patients with HCC.展开更多
Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the dia...Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.展开更多
AIM: To evaluate the benefit and effectiveness of MRarterioportography (MR-AP) to achieve the highest sensitivity for detection and evaluation of hepatocellular carcinoma (HCC). METHODS: Twenty liver cirrhosis patient...AIM: To evaluate the benefit and effectiveness of MRarterioportography (MR-AP) to achieve the highest sensitivity for detection and evaluation of hepatocellular carcinoma (HCC). METHODS: Twenty liver cirrhosis patients with suspected HCC were included before transarterial chemoembolization. In all patients double-enhanced Magnetic resonance imaging (MRI) was performed. A bolus of 10 mL Magnevist was injected through a selectively placed catheter in the superior mesenteric artery and MRI of the liver was performed in arterioportographic phase. Two independent readers evaluated number, size and localization of detected lesions. Diagnostic quality was determined using a 4-point scale. Differences were analyzed for significance using a t -test. Interobserver variability was calculated. RESULTS: In all 20 patients (100%), MR-AP was feasible. Diagnostic quality was, in all cases, between 1 and2 for both modalities and readers. MR-AP detected significantly more lesions than double-enhanced MRI (102.5 vs 61, respectively, P < 0.0024). The inter-observer variability was 0.881 for MRI and 0.903 for MR-AP. CONCLUSION: Our study confirmed that the MR-AP as an additional modality for detection of HCC is beneficial, as significantly more lesions were detected compared to MRI with liver-specific contrast.展开更多
Human stem cells are scalable cell populations capable of cellular differentiation.This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells.Such an approac...Human stem cells are scalable cell populations capable of cellular differentiation.This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells.Such an approach has the potential to improve our understanding of human biology and treating disease.In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases.In recent years,eff icient hepatic differentiation from human stem cells has been achieved by several research groups including our own.In this review we provide an overview of the f ield and discuss the future potential and limitations of stem cell technology.展开更多
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.
文摘AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.
基金Supported by NIHR Biomedical Research Centre funding scheme, Grants from the Higher Education Funding Council for Englandthe British Liver Trust and the Alan Morement Memorial Fund, Essex, United Kingdom the British Medical Association (Gunton Award)
文摘Hepatocellular carcinoma (HCC) is the commonest primary malignancy of the liver. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Orthotopic liver transplantation (OLT) is a suitable therapeutic option for early,unresectable HCC particularly in the setting of chronic liver disease. Following on from disappointing initial results,the seminal study by Mazzaferro et al in 1996 established OLT as a viable treatment for HCC. In this study,the "Milan criteria" were applied achieving a 4-year survival rate similar to OLT for benign disease. Since then various groups have attempted to expand these criteria whilst maintaining long term survival rates. The technique of living donor liver transplantation has evolved over the past decade,particularly in Asia,and published outcome data is comparable to that of OLT. This article will review the evidence,indications,and the future direction of liver transplantation for liver cancer.
文摘AIM: To investigate the capability of multidetector CT (MDCT) to diagnose HCC-associated arterioportal shunt (APS).METHODS: Two hundred and eighty-two patients with HCC received both thin-slice and enhancement MDCT scanning at early hepatic arterial phase, late hepatic arterial phase and portal venous phase, and digital subtract angiography (DSA) examination. Images were analyzed jointly by two experienced radiologists blinded to the opposite examination results, including the existence or not of APS, shunt locations, types and degrees of APS, with or without thrombosis. RESULTS: There were 56 APS associated with HCC, including 48 central, seven peripheral and one mixed, or 42 severe, seven moderate, seven mild APS. Fortyone severe, seven moderate and central APS were all revealed with MDCT and DSA. Seven mild and peripheral APS were all displayed with MDCT; only five of them displayed DSA, two faint shunt APS associated with massive HCC were missed. One mixed APS was demonstrated as severe combined with mild shunt with both MDCT and DSA.CONCLUSION: MDCT could diagnose not only DSA revealed APS, but also missed mild and peripheral APS with DSA due to faint shunt associated with massive HCC, is a simple, effective and noninvasive new technique for diagnosis of HCC-associated APS.
基金Supported by The National Natural Science Foundation of China,No.30270532 and No.30670774Tsinghua-Yue-Yuen Medical Science Foundation,No.20240000531 and No.20240000547
文摘AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a normal human liver cell line.METHODS： Net Ca^2＋ fluxes were measured with NMT, a technology that can obtain dynamic information of specific/selective ionic/molecular activities on material surfaces, non-invasively. The expression levels of TRPCl were increased by liposomal transfection, whose effectiveness was evaluated by Western-blotting and single cell reverse transcription-polymerase chain reaction.RESULTS： Ca^2＋ influxes could be elicited by adding 1 mmol/L CaCl2 to the test solution of HL-7702 cells. They were enhanced by addition of 20 μmol/L noradrenalin and inhibited by 100 μmol/L LaCl3 （a non-selective Ca^2＋ channel blocker）; 5 μmol/L nifedipine did not induce any change. Overexpression of TRPCl caused increased Ca^2＋ influx. Five micromoles per liter nifedipine did not inhibit this elevation, whereas 100 μmol/L LaCI3 did.CONCLUSION： In HL-7702 cells, there is a type of TRPCl-dependent Ca^2＋ channel, which could be detected v/a NMT and inhibited by La^3＋.
文摘AIM： To detect the DNA binding activity of nuclear factor-kappaB （NF-KB） in rat hepatocyte and to investigate the effects of NF-KB on rat hepatocyte regeneration and apoptosis after 70% portal branch Iigation. METHODS： Sixty Wistar rats were randomly divided into control group and portal branch ligation group. The animals were killed 12 h, 1, 2, 3, 7, and 14 d after surgery to determine the contents of plasma ALT. Hepatocytes were isolated and nuclear protein was extracted. DNA binding activity of NF-KB was measured by ENSA. Hepatocyte regeneration and apoptosis were observed under microscope by TUNEL staining. The ultrastructural changes of liver were observed under electron microscope. RESULTS： Seventy percent portal branch ligation produced atrophy of the ligated lobes and the perfused lobes underwent compensatory regeneration, the total liver weight and plasma ALT levels were maintained at the level of sham-operated animals throughout the experiment. After 2 d of portal branch ligation, DNA binding activity of NF-KB in hepatocyte increased and reached its peak, the number of apoptotic hepatocyte in the ligated lobes and the number of mitotic hepatocyte in the perfused lobes also reached their peak. Typical apoptotic changes and evident fibrotic changes in the ligated lobes were observed under electron microscope. CONCLUSION： After 70% portal branch ligation, DNA binding activity of NF-KB in hepatocyte is significantly increased and NF-KB plays an important role in hepatocyte regeneration and apoptosis.
文摘Objective： To investigate the relationship between the appearances of digital subtraction angiography （DSA） and the serum level of vascular endothelial growth factor （VEGF） in patients with primary hepatocellular carcinoma （HCC）. Methods： 24 HCC patients, 30 times DSA were examined, serum VEGF level was measured with the quantitative enzyme linked immunosorbent assay （ELISA） in patients and healthy control subjects in this study. Results： Among DSA for 24 patients with HCC, 18 of 24 cases showed hepatic artery blood supply of tumor. Four of 24 cases showed portal vein blood supply of tumor, 1 of 24 cases showed superior mesenteric artery blood supply of tumor and artery-venous shunt formation, and there was no blood supply to tumor in one case. Serum VEGF level in HCC[（χ＋s）194.5±14.2] ng/L was significant elevated to those in patients comparing with those of the normal controls （132.4±47.9） ng/L and marked differences （P〈0.01）. Conclusion： During the cases for plenty blood supply or arteryvenous shunt formation in patients with HCC, serum VEGF level markedly elevated in the patients of HCC. VEGF expression was significantly related to intrahepatic dissemination, recurrence and metastasis in patients with HCC.
基金Supported by The NIHR Biomedical Research Centre funding scheme and the following for authors’ funding and supportAIG is funded by a scholarship from the Egyptian Government+5 种基金SAK is supported by a grant from the Higher Education Funding Council for England (HEFCE)SDTR is funded by grants from the British Medical Research Council (MRC), London, United KingdomThe British Engineering, Physics and Science Research Council (EPSRC), Swindon, United KingdomThe Alan Morement Memorial Fund AMMF, Essex, United KingdomBroad Foundation, Los Angeles, United StatesPfizer Global Research and Development Inc, Sandwich, United Kingdom and GlaxoSmithKline, Ware, United Kingdom
文摘Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.
文摘AIM: To evaluate the benefit and effectiveness of MRarterioportography (MR-AP) to achieve the highest sensitivity for detection and evaluation of hepatocellular carcinoma (HCC). METHODS: Twenty liver cirrhosis patients with suspected HCC were included before transarterial chemoembolization. In all patients double-enhanced Magnetic resonance imaging (MRI) was performed. A bolus of 10 mL Magnevist was injected through a selectively placed catheter in the superior mesenteric artery and MRI of the liver was performed in arterioportographic phase. Two independent readers evaluated number, size and localization of detected lesions. Diagnostic quality was determined using a 4-point scale. Differences were analyzed for significance using a t -test. Interobserver variability was calculated. RESULTS: In all 20 patients (100%), MR-AP was feasible. Diagnostic quality was, in all cases, between 1 and2 for both modalities and readers. MR-AP detected significantly more lesions than double-enhanced MRI (102.5 vs 61, respectively, P < 0.0024). The inter-observer variability was 0.881 for MRI and 0.903 for MR-AP. CONCLUSION: Our study confirmed that the MR-AP as an additional modality for detection of HCC is beneficial, as significantly more lesions were detected compared to MRI with liver-specific contrast.
基金Supported by A RCUK fellowship,EP/E500145/1,to Hay DCA grant from the Edinburgh Bioquarter,to Medine CNChina Scholarship Council,No.2010658022,to Zhou WL
文摘Human stem cells are scalable cell populations capable of cellular differentiation.This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells.Such an approach has the potential to improve our understanding of human biology and treating disease.In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases.In recent years,eff icient hepatic differentiation from human stem cells has been achieved by several research groups including our own.In this review we provide an overview of the f ield and discuss the future potential and limitations of stem cell technology.
