Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan; Department of Immunology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
Haemophilia. 2014 Jan;20(1):e40-4. doi: 10.1111/hae.12311.
The use of induced pluripotent stem cells (iPSCs) 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 iPSCs for cell-based therapy of haemophilia. We generated iPSCs from mesenchymal stem cells that had been isolated from C57BL/6 mice. The mouse iPSCs were generated through the induction of four transcription factor genes Oct3/4, Klf-4, Sox-2 and c-Myc. The derived iPSCs released functional coagulation factor VIII (FVIII) following transduction with a simian immunodeficiency virus vector. The subcutaneous transplantation of iPSCs 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 iPSCs could be an attractive and prospective autologous cell source for the production of coagulation factor, and that engineered iPSCs expressing coagulation factor might provide a cell-based therapeutic strategy appropriate for haemophilia.
诱导多能干细胞（iPSCs）作为一种自体细胞来源，为许多遗传性疾病的细胞替代治疗带来了新的希望。我们专注于使用 iPSCs 进行基于细胞的血友病治疗。我们从 C57BL/6 小鼠分离的间充质干细胞中生成 iPSCs。通过诱导四个转录因子基因 Oct3/4、Klf-4、Sox-2 和 c-Myc，生成了小鼠 iPSCs。衍生的 iPSCs 在转导慢病毒载体后释放出功能性凝血因子 VIII（FVIII）。将表达 FVIII 的 iPSCs 皮下移植到裸鼠中导致畸胎瘤形成，并显著增加了 FVIII 的血浆水平。移植后 2-4 周，FVIII 的血浆浓度达到适合人类治疗的水平。我们的数据表明，iPSCs 可能是一种有吸引力的、有前景的自体细胞来源，可用于产生凝血因子，并且表达凝血因子的工程化 iPSCs 可能提供一种适合血友病的基于细胞的治疗策略。
