The increasing shortage of donors and the adverse effects of immunosuppression have restricted the impact of solid organ transplantation.Despite the initial promising developments in xenotransplantation,roadblocks sti...The increasing shortage of donors and the adverse effects of immunosuppression have restricted the impact of solid organ transplantation.Despite the initial promising developments in xenotransplantation,roadblocks still need to be overcome and this form of organ support remains a long way from clinical practice.While hepatocyte transplantation may be effectively correct metabolic defects,it is far less effective in restoring liver function than liver transplantation.Tissue engineering,using extracellular matrix scaffolds with an intact but decellularized vascular network that is repopulated with autologous or allogeneic stem cells and/or adult cells,holds great promise for the treatment of failure of organs within gastrointestinal tract,such as endstage liver disease,pancreatic insufficiency,bowel failure and type 1 diabetes.Particularly in the liver field,where there is a significant mortality of patients awaiting transplant,human bioengineering may offer a source of readily available organs for transplantation.The use of autologous cells will mitigate the need for long term immunosuppression thus removing a major hurdle in transplantation.展开更多
AIM: To investigate the use of Daclizumab (Dmab) as an immunosuppressive agent in an experimental model of hepatocyte xenotransplantation (XenoTx) in rats with fulminant hepatic failure (FHF). METHODS: Two white male ...AIM: To investigate the use of Daclizumab (Dmab) as an immunosuppressive agent in an experimental model of hepatocyte xenotransplantation (XenoTx) in rats with fulminant hepatic failure (FHF). METHODS: Two white male New Zealand rabbits were used as donors and 68 Wistar rats as recipients. FHF was induced by intravenous application of dimethylnitrosamine (DMNA). The isolated hepatocytes of the rabbits were xenotransplanted into the spleen of the rats 24 h after FHF induction. Group A (n = 13): no treatment; Group B (n = 14): FHF and XenoTx; Group C (n = 14): FHF and XenoTx and cyclosporin (CsA); Group D (n = 14): FHF and XenoTx and Dmab; Group E (n = 13): FHF and XenoTx and CsA and Dmab. The rats were followed for 15 d. RESULTS: Statistical analysis showed better survival among groups D (92.86%) and E (76.92%) compared to group A (all rats died after 72 h), group B (28.57%) or group C (71.43%), although the differences were not statistically significant. Biochemical evaluation of the liver enzymes and histology confirmed satisfactory function and engraftment, respectively. CONCLUSION: This experimental model has shown the safe, effective and beneficial use of Dmab in a xenotransplantation model of rabbit hepatocytes in rats.展开更多
Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was e...Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.展开更多
Functional human hepatocytes xenografted into the liver of mice can be used as a model system to study pharmacokinetics,infection of hepatitis viruses,and the efficacy of hepatitis vaccines.Significant levels of liver...Functional human hepatocytes xenografted into the liver of mice can be used as a model system to study pharmacokinetics,infection of hepatitis viruses,and the efficacy of hepatitis vaccines.Significant levels of liver xeno-repopulation have been reported in Fah-/-Rag2-/-Il2rg-/-mice.However,the high mortality and low breeding rate of this model may hinder its application.A new model,termed Fah-/-Nod/Scid mice,which combines the advantages of liver repopulation in Fah-/-mice with the ease of xenotransplantation in Nod/Scid mice was obtained by gradual cross-breeding.Fah-/-Nod/Scid mice were easily maintained in breeding colonies and in adult animal care facilities.FK506 treatment combined with gradual withdrawal of NTBC before cell transplantation ensured that Fah-/-Nod/Scid mice were susceptible to liver xeno-repopulation by human hepatocytes;the proportion of engrafted human hepatocytes reached 33.6%.The function of the expanded human hepatocytes within the chimeric liver was confirmed by weight curve analysis,the expression of characteristic proteins,and the biochemical analysis of liver function.These results show that Fah-/-Nod/Scid mice are an ideal humanized liver mouse model with many useful applications.展开更多
Background:Hepatocellular carcinoma(HCC)is frequently associated withmetabolism dysfunction.Increasing evidence has demonstrated the crucial role of lipidmetabolismin HCC progression.The function of apolipoprotein F(A...Background:Hepatocellular carcinoma(HCC)is frequently associated withmetabolism dysfunction.Increasing evidence has demonstrated the crucial role of lipidmetabolismin HCC progression.The function of apolipoprotein F(ApoF),a lipid transfer inhibitor protein,in HCC is incompletely understood.We aimed to evaluate the functional role of ApoF in HCC in this study.Methods:We used quantitative reverse-transcription polymerase chain reaction(qRT-PCR)to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines(SMMC-7721,HepG2,and Huh7).Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues.The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed.The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo.Results:ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues.In SMMC-7721 and Huh7 HCC cells,ApoF overexpression inhibited cell proliferation and migration.In a xenograft nude mouse model,ApoF overexpression effectively controlled HCC growth.Kaplan–Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients.Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis,Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage.Conclusions:ApoF expression was down-regulated in HCC,which was associated with low recurrence-free survival rate.ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease.展开更多
文摘The increasing shortage of donors and the adverse effects of immunosuppression have restricted the impact of solid organ transplantation.Despite the initial promising developments in xenotransplantation,roadblocks still need to be overcome and this form of organ support remains a long way from clinical practice.While hepatocyte transplantation may be effectively correct metabolic defects,it is far less effective in restoring liver function than liver transplantation.Tissue engineering,using extracellular matrix scaffolds with an intact but decellularized vascular network that is repopulated with autologous or allogeneic stem cells and/or adult cells,holds great promise for the treatment of failure of organs within gastrointestinal tract,such as endstage liver disease,pancreatic insufficiency,bowel failure and type 1 diabetes.Particularly in the liver field,where there is a significant mortality of patients awaiting transplant,human bioengineering may offer a source of readily available organs for transplantation.The use of autologous cells will mitigate the need for long term immunosuppression thus removing a major hurdle in transplantation.
文摘AIM: To investigate the use of Daclizumab (Dmab) as an immunosuppressive agent in an experimental model of hepatocyte xenotransplantation (XenoTx) in rats with fulminant hepatic failure (FHF). METHODS: Two white male New Zealand rabbits were used as donors and 68 Wistar rats as recipients. FHF was induced by intravenous application of dimethylnitrosamine (DMNA). The isolated hepatocytes of the rabbits were xenotransplanted into the spleen of the rats 24 h after FHF induction. Group A (n = 13): no treatment; Group B (n = 14): FHF and XenoTx; Group C (n = 14): FHF and XenoTx and cyclosporin (CsA); Group D (n = 14): FHF and XenoTx and Dmab; Group E (n = 13): FHF and XenoTx and CsA and Dmab. The rats were followed for 15 d. RESULTS: Statistical analysis showed better survival among groups D (92.86%) and E (76.92%) compared to group A (all rats died after 72 h), group B (28.57%) or group C (71.43%), although the differences were not statistically significant. Biochemical evaluation of the liver enzymes and histology confirmed satisfactory function and engraftment, respectively. CONCLUSION: This experimental model has shown the safe, effective and beneficial use of Dmab in a xenotransplantation model of rabbit hepatocytes in rats.
基金supported by Department of Oncology, the Affiliated Hospital of Qingdao University, China
文摘Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.
基金supported by the National High Technology Research and Development Program of China(Grant No. 2006AA02Z474)the National Natural Science Foundation of China(Grant No. 30801115)+1 种基金the China Postdoctoral Science Foundation(Grant No. 20070410743)the National Basic Research Program of China(Grant No. 2010CB945600)
文摘Functional human hepatocytes xenografted into the liver of mice can be used as a model system to study pharmacokinetics,infection of hepatitis viruses,and the efficacy of hepatitis vaccines.Significant levels of liver xeno-repopulation have been reported in Fah-/-Rag2-/-Il2rg-/-mice.However,the high mortality and low breeding rate of this model may hinder its application.A new model,termed Fah-/-Nod/Scid mice,which combines the advantages of liver repopulation in Fah-/-mice with the ease of xenotransplantation in Nod/Scid mice was obtained by gradual cross-breeding.Fah-/-Nod/Scid mice were easily maintained in breeding colonies and in adult animal care facilities.FK506 treatment combined with gradual withdrawal of NTBC before cell transplantation ensured that Fah-/-Nod/Scid mice were susceptible to liver xeno-repopulation by human hepatocytes;the proportion of engrafted human hepatocytes reached 33.6%.The function of the expanded human hepatocytes within the chimeric liver was confirmed by weight curve analysis,the expression of characteristic proteins,and the biochemical analysis of liver function.These results show that Fah-/-Nod/Scid mice are an ideal humanized liver mouse model with many useful applications.
基金This study was supported by grants from the National Natural Science Foundation of China[No.81572726]the Natural Science Foundation of Guangdong Province[No.2018A030313641 and No.2016A030313848]+1 种基金the Science and Technology Planning Project of Guangdong Province[No.2014A020212122 and No.2016A020212004]the Medical Research Foundation of Guangdong Province[No.A2016312].
文摘Background:Hepatocellular carcinoma(HCC)is frequently associated withmetabolism dysfunction.Increasing evidence has demonstrated the crucial role of lipidmetabolismin HCC progression.The function of apolipoprotein F(ApoF),a lipid transfer inhibitor protein,in HCC is incompletely understood.We aimed to evaluate the functional role of ApoF in HCC in this study.Methods:We used quantitative reverse-transcription polymerase chain reaction(qRT-PCR)to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines(SMMC-7721,HepG2,and Huh7).Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues.The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed.The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo.Results:ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues.In SMMC-7721 and Huh7 HCC cells,ApoF overexpression inhibited cell proliferation and migration.In a xenograft nude mouse model,ApoF overexpression effectively controlled HCC growth.Kaplan–Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients.Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis,Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage.Conclusions:ApoF expression was down-regulated in HCC,which was associated with low recurrence-free survival rate.ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease.
