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- W2567415079 abstract "Hemophilia A is an inherited bleeding disorder caused by a deficiency of the procoagulant cofactor VIII (FVIII). Currently, the patients with hemophilia A are being treated through repeated intravenous injection of FVIII concentrates. Since FVIII is a secreted protein and the tight regulation of its expression is not necessary, ex vivo gene therapy strategies for hemophilia A might be good for the therapeutic alternative. We previously demonstrated that therapeutic levels of plasma FVIII were documented from hemophilia A mice over 300 days, in which lentivirally-engineered blood outgrowth endothelial cells (BOECs) sheet were implanted subcutaneously (Tatsumi K et.al. PLoS One 2013 8(12):e83280). To enhance the viability of the implanted BOECs which boost the FVIII expression, double-layered cell sheets transplantation was performed by placing the recovered BOECs sheet onto the fibroblast sheet directly. FVIII transduced BOECs and non-transduced fibroblasts were cultured on temperature-responsive culture dish independently. Both cells were recovered as a contiguous cell sheet. Subcutaneous co-transplantation studies of BOEC and fibroblast sheet indicated that all hemophilia A mice treated with cyclophosphamide expressed between 40-50 mU/mL levels of FVIII without developing anti-FVIII inhibitory antibodies over 200 days. In contrast, the hemophilia A mice without any prior immuno-suppressive treatment developed neutralizing anti-FVIII antibodies between 5-10 Bethesda units. These therapeutic FVIII levels were two times higher than the group of hemophilia A mice that were transplanted BOECs sheet alone. Histological examination in the part of the mice revealed that the combination of BOEC and fibroblast sheet was structured as flat clusters without any cells infiltration. In conclusion, tissue engineering approach using double-layered cell sheets are viable for persistent tissue survival and providing therapeutic values. This novel ex vivo gene transfer strategy can provide the safe and efficacious delivery of FVIII in hemophilia A and merits further assessment." @default.
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- W2567415079 date "2015-05-01" @default.
- W2567415079 modified "2023-10-16" @default.
- W2567415079 title "175. Double-Layered Cell Sheets Transplantation That Achieves Durable Factor VIII Delivery in the Mouse Model of Hemophilia A" @default.
- W2567415079 doi "https://doi.org/10.1016/s1525-0016(16)33780-7" @default.
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