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• W2002204102 abstract "Background— Although human embryonic stem cells (hESC) have enormous potential for cell replacement therapy of heart failure, immune rejection of hESC derivatives inevitably would occur after transplantation. We therefore aimed to generate a hypoantigeneic hESC line with improved survival characteristics. Methods and Results— Using various in vivo, nonischemic, hindlimb xenotransplant models (immunocompetent and defined immunodefective mouse strains) as well as human in vitro T-cell and natural killer (NK)-cell assays, we revealed a central role for T cells in mediating hESC rejection. The NK-cell susceptibility of hESC in vivo was found to be low, and the NK response to hESC challenge in vitro was negligible. To reduce the antigenicity of hESC, we successfully generated human leukocyte antigen (HLA) I knockdown cells (hESC siRNA+IB ) using both HLA I RNA interference (siRNA) and intrabody (IB) technology. HLA I expression was ≈99% reduced after 7 days and remained low for weeks. Cellular immune recognition of these hESC siRNA+IB was strongly reduced in both xenogeneic and allogeneic settings. Immune rejection was profoundly mitigated after hESC siRNA+IB transplantation into immunocompetent mice, and even long-term graft survival was achieved in one third of the animals without any immunosuppression. The survival benefit of hESC siRNA+IB was further confirmed under ischemic conditions in a left anterior descending coronary artery ligation model. Conclusions— HLA I knockdown hESC siRNA+IB provoke T-cell ignorance and experience largely mitigated xenogeneic rejection. By generating hypoantigeneic hESC lines, the generation of acceptable hESC derivatives may become a practical concept and push cell replacement strategies forward." @default.
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• W2002204102 date "2011-09-13" @default.
• W2002204102 modified "2023-10-14" @default.
• W2002204102 title "Human Leukocyte Antigen I Knockdown Human Embryonic Stem Cells Induce Host Ignorance and Achieve Prolonged Xenogeneic Survival" @default.
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• W2002204102 doi "https://doi.org/10.1161/circulationaha.111.020727" @default.
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