Disease Modeling for Mitochondrial Disease Using MELAS Specific Induced Pluripotent Stem Cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860623
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Keio University
• Principal Investigator: KODAIRA Masaki 慶應義塾大学, 医学部, 助教 (70464865)
• Research Collaborator: YUASA Shinsuke 慶應義塾大学, 医学部, 講師 (90398628) ; EGASHIRA Toru 慶應義塾大学, 医学部, 助教 (10465023) ; HASHIMOTO Hisayuki 慶應義塾大学, 医学部, 助教 (90528390) ; KUSUMOTO Dai 慶應義塾大学, 医学部, 助教 (70571727) ; KUNITOMI Akira 慶應義塾大学, 医学部, 助教 (30570882) ; KASHIMURA Shin 慶應義塾大学, 医学部, 助教 (90571125)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ミトコンドリア病 / iPS細胞 / 疾患解析

Outline of Final Research Achievements

We successfully established iPSCs from MELAS- fibroblasts. MELAS is one of the most common mitochondrial disease and there are no effective ways to cure the disease at the moment. MELAS-iPSC lines ranged from 3.6% to 99.4% of m.3243A>G heteroplasmy levels. The enzymatic activities of mitochondrial respiratory complexes indicated that MELAS-iPSC-derived fibroblasts with high heteroplasmy levels showed a deficiency of complex I activity but MELAS-iPSC-derived fibroblasts with low heteroplasmy levels showed normal complex I activity. Our data indicate that MELAS-iPSCs can be models for MELAS but we should carefully select MELAS-iPSCs with appropriate heteroplasmy levels and respiratory functions for mitochondrial disease modeling.

Free Research Field

人文