Development of novel thymus-directed strategy for central immune tolerance induction in hemophilia A

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591430
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Jichi Medical University
• Principal Investigator: MADOIWA Seiji 自治医科大学, 医学部, 講師 (70296119)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Eiji 自治医科大学, 医学部, 客員教授 (00245044) ; OHMORI Tsukasa 自治医科大学, 医学部, 講師 (70382843)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 血友病 / インヒビター / 免疫寛容 / 人工多能性幹細胞 / 遺伝子治療 / 細胞移植療法 / 胸腺上皮細胞

Outline of Final Research Achievements

Hemophilia A is an X-linked, recessive hereditary bleeding disorder due to deficient coagulation factor VIII (FVIII). However, about 30% of patients with severe deficiency develop inhibitors or circulating alloantibodies against infused factor VIII. Once an inhibitor develops, treatment of bleeding episodes is quite difficult due to partial or complete lack of efficacy of replacement therapy. Immune tolerance induction (ITI) by prolonged administration of FVIII concentrates is currently the only therapy proven to eliminate persistent inhibitors in severe hemophilia A. In this project, we investigated central ITI by thymic implantation of epithelial progenitor cells derived from induced pluripotent stem (iPS) cells, which will be isolated from fibroblasts of congenic hemophilia A mice and transduced with the SIV encoding FVIII.

Free Research Field

医歯薬学