Treatment of epidermolysis bullosa with revertant keratinocyte-derived iPS cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09753
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: Fujita Yasuyuki 北海道大学, 大学病院, 講師 (80374437)
• Co-Investigator(Kenkyū-buntansha): 清水 宏 北海道大学, 医学研究院, 教授 (00146672) ; 乃村 俊史 北海道大学, 大学病院, 講師 (50399911) ; 夏賀 健 北海道大学, 大学病院, 講師 (70645457)
• Research Collaborator: MATSUMURA WAKANA 北海道大学, 大学院医学院, 大学院生 ; NAKAYAMA CHIHIRO 北海道大学, 大学院医学院, 大学院生
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 表皮水疱症

Outline of Final Research Achievements

Cell-based therapies such as allogeneic mesenchymal stem/stromal cells (MSCs) transplantation for recessive dystrophic epidermolysis bullosa (RDEB) were explored. However, some hurdles exist to come over in current MSC-based therapies; limited proliferation and limited cell survival. To solve these problems, we focused on keratinocyte-derived induced pluripotent stem cells (iPSCs). Keratinocytes from intact areas of patients might have revertant mosaicism where the pathogenic mutations are spontaneously corrected. In this study, we succeeded to develop MSCs from keratinocytes-derived iPSCs (KC-iPSC-MSCs) of normal human and a RDEB patient. Keratinocytes-derived iPSCs (KC-iPSCs) were cultured with activin A, BIO and BMP4 to induct mesoderm lineage, and then cultured with bFGF and EGF. In 14 days, spindle-shaped cells
appeared which showed mesenchymal differentiation. Furthermore, the intravenous injection of the KC-iPSC-MSCs into wounded mice induced human type VII collagen.

Free Research Field

皮膚科学