Cell-based Therapies Toward Hemophilia Using Autologous Cells from Hemophilic Individuals

2015 Fiscal Year Final Research Report

• Project/Area Number: 24300174
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Osaka University (2014-2015); Nara Medical University (2013); Tokyo Women's Medical University (2012)
• Principal Investigator: OHASHI KAZUO 大阪大学, 薬学研究科(研究院), 教授 (40364062)
• Co-Investigator(Kenkyū-buntansha): SUGIMOTO Mitsuhiko 奈良県立医科大学, 医学部, 教授 (80192128) ; NAKAYAMA Masamichi 東京女子医科大学, 医学部薬, 講師 (00338980)
• Co-Investigator(Renkei-kenkyūsha): MIZUGUCHI Hiroyuki 大阪大学, 薬学研究科, 教授 (50311387) ; IWATA Hiroo 京都大学, 再生医科学研究所, 教授 (30160120)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 再生医療 / 血友病 / 細胞遺伝子治療 / 血液凝固因子

Outline of Final Research Achievements

This project aimed to create cell-based therapy toward hemophilia. Basic concept of this project is to proliferate patient's own cells with the genetic modification using viral vectors. Hepatocytes and blood outgrowth endothelial cells (BOECs) were used. For hepatocyte proliferation, we isolated hemophilic hepatocytes from factor IX-knockout mice which were then transplanted into uPA/SCID mouse livers. After the transplantation, the hemophilic hepatocytes had been actively proliferated to fully reconstitute uPA/SICD mouse livers. Injecting AAV vectors into the uPA/SCID mice resulted in high level of FIX gene transduction to the reconstituted hemophilic hepatocytes within the liver. The genetically-modified hemophilic hepatocytes were subsequently recovered, followed by their transplantation back into the hemophilic individuals. The present study also utilized blood outgrowth endothelial cells established from factor IX-knockout mice for FIX gene transduction.

Free Research Field

消化器外科　再生医療