With their ability to undergo unlimited self-renewal in culture and to differentiate into all cell types in the body, human embryonic stem ceils （hESCs） hold great potential for the treatment of currently incurable ...With their ability to undergo unlimited self-renewal in culture and to differentiate into all cell types in the body, human embryonic stem ceils （hESCs） hold great potential for the treatment of currently incurable diseases. Two hESC-based cell therapies for spinal cord injury and macular degeneration have been advanced into human clinical trials. Despite this rapid progress, one key challenge of hESC-based cell therapy is the allogeneic immune rejection of hESC-derived cells by recipients. This problem could be mitigated by a recent breakthrough in the technology of induced pluripotent stem cells （iPSCs） by nuclear reprogramming of patient-specific somatic cells with defined factors, which could become a renewable source of autologous ceils for cell therapy. However, recent studies revealing the abnormal epigenetics, genomic stability and immunogenicity of iPSCs have raised safety concerns over iPSC-based therapy. Recent findings related to the immunogenicity of iPSC derivatives will be summarized in this review.展开更多
<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is str...<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14</span><span> </span><span>-</span><span> </span><span>30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group </span><span>showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 </span><span>as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2</span><i><span>α</span></i><span>R and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significant</span><span>ly</span><span> positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR w</span><span>as</span><span> clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.</span> </p>展开更多
Background Loss of carcinoembryonic antigen-related cell adhesion molecule 1 （CEACAM1） expression is an adverse prognostic factor in hepatocellular carcinoma （HCC）. The purpose of this study was to investigate the...Background Loss of carcinoembryonic antigen-related cell adhesion molecule 1 （CEACAM1） expression is an adverse prognostic factor in hepatocellular carcinoma （HCC）. The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival （RFS） following liver transplantation （LT） for HCC. Methods Expression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed. Results Of the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum （z-fetoprotein levels （all P 〈0.05）. Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis （P=0.027）. Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation （P=0.037）. Conclusion Loss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.展开更多
目的了解供肝复流后细胞增殖周期的变化,明确药物预处理和缺血预处理对其的影响.方法建立大鼠三袖套法原位肝移植模型,观察移植肝细胞复流前后不同时间增殖细胞核抗原的表达情况;对供肝分别作药物预处理和缺血预处理,比较正常肝、预处...目的了解供肝复流后细胞增殖周期的变化,明确药物预处理和缺血预处理对其的影响.方法建立大鼠三袖套法原位肝移植模型,观察移植肝细胞复流前后不同时间增殖细胞核抗原的表达情况;对供肝分别作药物预处理和缺血预处理,比较正常肝、预处理供肝和未预处理供肝复流2 h 后的增殖细胞核抗原、肝酶谱及肝细胞凋亡状况.结果移植肝细胞复流2 h 后增殖细胞核抗原表达显著增高,12 h 后恢复正常水平;正常肝、药物预处理供肝、缺血预处理供肝、未预处理供肝复流2 h 后的增殖细胞核抗原表达和肝酶谱依次升高,PCNA(%):2.1±0.1,4.3±0.2,7.0±0.4,9.4±0.4,AST(nKat·L^(-1)):3.5±1.6,28.1±11.9,53.8±12.3,75.2±24.1,ALT(nKat·L^(-1)):2.8±2.7,46.1±17.6,61.7±22.9,90.5±30.1,LDH(nKat·L^(-1)):49.6±7.6,61.4±15.3,95.4±23.2,148.3±30.1.结论供肝复流后肝细胞 G_1期缩短至2 h 以内,整个细胞周期时间缩短至20 h 左右.正常肝、药物预处理供肝、缺血预处理供肝、未预处理供肝肝损害程度依次加重,整个细胞周期时间依次缩短.展开更多
文摘With their ability to undergo unlimited self-renewal in culture and to differentiate into all cell types in the body, human embryonic stem ceils （hESCs） hold great potential for the treatment of currently incurable diseases. Two hESC-based cell therapies for spinal cord injury and macular degeneration have been advanced into human clinical trials. Despite this rapid progress, one key challenge of hESC-based cell therapy is the allogeneic immune rejection of hESC-derived cells by recipients. This problem could be mitigated by a recent breakthrough in the technology of induced pluripotent stem cells （iPSCs） by nuclear reprogramming of patient-specific somatic cells with defined factors, which could become a renewable source of autologous ceils for cell therapy. However, recent studies revealing the abnormal epigenetics, genomic stability and immunogenicity of iPSCs have raised safety concerns over iPSC-based therapy. Recent findings related to the immunogenicity of iPSC derivatives will be summarized in this review.
文摘<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14</span><span> </span><span>-</span><span> </span><span>30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group </span><span>showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 </span><span>as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2</span><i><span>α</span></i><span>R and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significant</span><span>ly</span><span> positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR w</span><span>as</span><span> clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.</span> </p>
文摘Background Loss of carcinoembryonic antigen-related cell adhesion molecule 1 （CEACAM1） expression is an adverse prognostic factor in hepatocellular carcinoma （HCC）. The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival （RFS） following liver transplantation （LT） for HCC. Methods Expression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed. Results Of the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum （z-fetoprotein levels （all P 〈0.05）. Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis （P=0.027）. Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation （P=0.037）. Conclusion Loss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.
文摘目的了解供肝复流后细胞增殖周期的变化,明确药物预处理和缺血预处理对其的影响.方法建立大鼠三袖套法原位肝移植模型,观察移植肝细胞复流前后不同时间增殖细胞核抗原的表达情况;对供肝分别作药物预处理和缺血预处理,比较正常肝、预处理供肝和未预处理供肝复流2 h 后的增殖细胞核抗原、肝酶谱及肝细胞凋亡状况.结果移植肝细胞复流2 h 后增殖细胞核抗原表达显著增高,12 h 后恢复正常水平;正常肝、药物预处理供肝、缺血预处理供肝、未预处理供肝复流2 h 后的增殖细胞核抗原表达和肝酶谱依次升高,PCNA(%):2.1±0.1,4.3±0.2,7.0±0.4,9.4±0.4,AST(nKat·L^(-1)):3.5±1.6,28.1±11.9,53.8±12.3,75.2±24.1,ALT(nKat·L^(-1)):2.8±2.7,46.1±17.6,61.7±22.9,90.5±30.1,LDH(nKat·L^(-1)):49.6±7.6,61.4±15.3,95.4±23.2,148.3±30.1.结论供肝复流后肝细胞 G_1期缩短至2 h 以内,整个细胞周期时间缩短至20 h 左右.正常肝、药物预处理供肝、缺血预处理供肝、未预处理供肝肝损害程度依次加重,整个细胞周期时间依次缩短.
