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Production of functional coagulation factor VIII from iPSCs using a lentiviral vector
Author(s) -
Kashiwakura Y.,
Ohmori T.,
Mimuro J.,
Madoiwa S.,
Inoue M.,
Hasegawa M.,
Ozawa K.,
Sakata Y.
Publication year - 2014
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.12311
Subject(s) - induced pluripotent stem cell , medicine , viral vector , genetic enhancement , cancer research , haemophilia , transplantation , factor ix , mesenchymal stem cell , coagulation , immunology , embryonic stem cell , biology , pathology , gene , surgery , genetics , recombinant dna
Summary The use of induced pluripotent stem cells ( iPSC s) as an autologous cell source has shed new light on cell replacement therapy with respect to the treatment of numerous hereditary disorders. We focused on the use of iPSC s for cell‐based therapy of haemophilia. We generated iPSC s from mesenchymal stem cells that had been isolated from C57BL/6 mice. The mouse iPSC s were generated through the induction of four transcription factor genes Oct3/4, Klf‐4, Sox‐2 and c‐Myc. The derived iPSC s released functional coagulation factor VIII (FVIII) following transduction with a simian immunodeficiency virus vector. The subcutaneous transplantation of iPSC s expressing FVIII into nude mice resulted in teratoma formation, and significantly increased plasma levels of FVIII. The plasma concentration of FVIII was at levels appropriate for human therapy at 2–4 weeks post transplantation. Our data suggest that iPSC s could be an attractive and prospective autologous cell source for the production of coagulation factor, and that engineered iPSC s expressing coagulation factor might provide a cell‐based therapeutic strategy appropriate for haemophilia.